Bringing Hope for Better Health through the Infinite Power of Science

Company Overview
Orizuru Therapeutics promotes the social implementation of cell therapy products andinnovative iPS cell-related technologies (platform innovation).

We are an R&D-driven company, focusing on the development of iPS cell-based regenerative
medicine and the application of iPS cell technologies.
In 2015, the Center for iPS Cell Research and Application (CiRA), Kyoto University and Takeda
Pharmaceutical Company Limited launched the joint research program T-CiRA to accelerate the researchand advancement of iPS cell technologies as well as its application in regenerative medicine and drug
development. In 2021, Orizuru Therapeutics Inc. was established for the purpose of transferring some of
their outcomes into clinical practices as sustainable business.
Our portfolio was initially focused on two potential therapies researched under the T-CiRA program.
One was with iPS cell-derived cardiomyocytes led by Project Leader Yoshinori Yoshida (AssociateProfessor at CiRA) and the other was iPS cell-derived pancreatic islet cells led by Project Leader TaroToyoda (Junior Associate Professor at CiRA). We will continue to seek other potential therapy whereiPS cell technology may play a critical role. Another business scope is to support any drug discovery
research activities and to build an iPS cell research platform based on our advancing iPS cell technologies.
Even though we have just started, we are comprised of over 50 staff who are either best-in-classresearchers or with in-depth expertise as technicians in the latest iPS cell technologies. We have a mind
in young, open, and free, yet our heart is "to help society and patients per iPS cell technologies comefrom Japan." This is the origin of our company's name, Orizuru.
We inherit the scientific technologies of CiRA and Takeda, and will build new cultures on top of these
here at Shonan iPark campus, Kanagawa, Japan. By providing regenerative medicines, we will contributeto the future for medical practice, our people, and our society.

Kenji Nonaka
M.D., Ph.D.
President, Representative Director and CEO ofOrizuru Therapeutics, Inc.
Qualifications

1990: Graduate Kyorin University, School of Medicine, andobtained Medical License
2002: Doctor Degree

Scope ofBusiness

1. Development of regenerative medical products through cell transplantation.
2. Support for drug discovery research and development of regenerative medicine
research infrastructure by utilizing iPS cell-related technologies.

Company Name

Orizuru Therapeutics, Inc.

FoundedApril 9, 2021

Address

2-26-1 Muraoka-higashi, Fujisawa-shi, Kanagawa, 251-8555 Japan

Representative
Director

Kenji Nonaka

AccessLocation: Shonan Health Innovation Park, 2-26-1 Muraoka-higashi, Fujisawa-shi, Kanagawa,251-8555 Japan

By train

By carFrom JR Ofuna Station: Take the Enoden Bus toward
Fujisawa Station Kitaguchi (bus stop No. 1 at the East
Exit bus terminal south of Lumine Wing) and get off atShonan iPark. (Approx. 15 mins)
From JR Fujisawa Station: Take the Enoden Bus toward
Ofuna Station Higashiguchi Shiki-no Mori (bus stop No. 9at the North Exit bus terminal) and get off at Shonan
iPark. (Approx. 15 mins)

From Tokyo: About 11 km from theKamiyabe Interchange on the Yokohama
Bypass (Yokohama Shindo) via Route 1
Harajuku
From Odawara: About 6 km from theFujisawa Interchange on theShin-Shonan Bypass via Fujisawa-Bashi1Shonan Bypass

Orizuru Therapeutics, Inc.

Ofu
Stat naion

Message from CEOBusiness career

1990-1994: Resident, Kyorin University Hospital, Department ofThoracic Surgery
1994-1996: Chief Resident, TORANOMON Hospital, Tokyo,Japan,
1996-1999: Staff, Kyorin University Hospital, Department ofCardiovascular Surgery, Tokyo Japan,
1999-2001: Instructor, Baylor College of Medicine, Departmentof Surgery, Houston, TX,
2002-2008: Research Director, Research Development Center,Banyu Pharmaceutical K.K. Tokyo Japan,
2008-2011: Director, Clinical R&D Department, Abbott
Laboratories, Tokyo Japan,
2011-2016: Director, Head of Japan R&D, Abbvie Inc., TokyoJapan,
2016-2021: Vice President, Head of Japan R&D, Janssen
Pharmaceutical K.K., Tokyo Japan,

Junction of Fujisawa

Fujisawa
StationShonan Health Innovation Parkhttps://orizuru-therapeutics.com/en/

Orizuru Therapeutics Inc.

Our Business

Bringing Hope for Better Health through the Infinite Power of Science

iCM Project

iPIC Project

Platform Innovation

We are developing a definitive therapy for severe heart failure patients with limited
therapeutic options.

We are developing a definitive therapy for brittle type 1 diabetes patients who are unable
to control their blood glucose level.

We promote innovation in drug discovery research and development of regenerative
medicine by utilizing cutting-edge iPS cell technology.

What is iCM

What is iPIC

Platform Innovation by Orizuru Therapeutics

iCM is a human iPS cell-derived cardiomyocyte created by a T-CiRA's project led by Dr. Yoshinori Yoshida,
Associate Professor at CiRA, Kyoto University. The myocardial differentiation method, which has beenstudied at CiRA, has been further improved toward practical use by utilizing the cardiomyocytes purification
method with small molecule compounds discovered in the T-CiRA program. By transplanting iCMs,
highly engraftable, pure, and safe cardiomyocytes, into the patient's heart, they are expected to replenish
the cardiomyocytes lost as the disease progresses and promote remuscularization. Restoring the cardiac
function of patients with severe heart failure, which has been considered difficult to treat, can be expected toimprove the quality of life (QOL) and prognosis of these patients.

iPICs are human iPS cell-derived pancreatic islet cells expected to be suitable for cell therapy. They werediscovered after a five-year optimization study through T-CiRA based on the pancreatic cell differentiation
method (Stem Cell Res. 2015;14:185-97) discovered by Dr. Taro Toyoda, Junior Associate Professor atCiRA. iPIC is an aggregate of highly-purified pancreatic endocrine cells that contains both insulin andNKX6.1 positive cells, a characteristic of pancreatic β cells. After implantation in vivo, pancreatic islet-likestructures containing glucagon positive cells, another important endocrine cell type, are formed, andphysiological insulin-secreting capabilities can be demonstrated in response to glucose loading andhypoglycemia.

A variety of iPS cell differentiation technologies and the related technologies cultivated through theTakeda-CiRA Joint Program for iPS Cell Applications (T-CiRA) and many researchers and specialists who
can comprehensively utilize the technologies have been consolidated at Orizuru Therapeutics. With such
unique organizational advantage, Orizuru Therapeutics will develop and improve a new drug discovery
support platform to accelerate discovery of innovative pharmaceutical products (disease-specific iPS celldifferentiation technology, organoid technology). Additionally, a new medical research platform for researchand development and clinical application of iPS cell-derived cell therapy products (original iPS cell platform
including hypoimmunogenic iPS cell line) to promote the use of iPS cell technology in society.

Engraftment of implanted cellin rat myocardial infarction model

Engraftment of implanted cellin monkey myocardial infarction model
Graft

iPIC before implantation

iPIC after implantation

Human cadaveric
pancreatic islets

A variety of iPS cell differentiation technologies

Abundant analysis technologies of celluklar function

Graft

Maturationin vivo

Our strength
Research and development of regenerative medical products using iCM
Cardiomyocyte therapy requires the delivery of hundreds of millions of cardiomyocytes or more topatients. To provide cell products to patients with severe heart failure who are awaiting treatment, it isnecessary to develop cell manufacturing technologies that can efficiently produce large numbers of cells.
One of the most important technologies is a culture technique in which cells are suspended in a mediumand cultured. Since the early stage of development, we have been working on a method for cardiomyocyte
differentiation using a suspension culture system, which has been considered difficult to obtain highquality cardiomyocytes. In addition, we have discovered unique small molecule compounds that efficiently
remove non-cardiomyocytes generated during cardiac differentiation. By combining these state-of-art
technologies with the differentiation method for preparing highly engraftable cardiomyocytes found in
CiRA, high-performance, safe iCMs can be produced with a simple differentiation process. iCMs arehighly effective when administered as single cells, eliminating the need for sheet or aggregate reformation.
In addition, iCM is suitable for a wide range of administration methods, including catheter administration,
enabling minimally invasive treatment with less burden on the patient.
iPS cells

Solution
Solutionprovidedwithby iPS
iCM
cell-derived
cardiomyocyte(iCM)

Stable supply
and off-the-shelf treatment
with the mass
production-frien
dly allo-iPS cells

iPS cell-derived
cardiomyocyte

Achievement of both
high productivity andhigh-purity. Mass
production-friendly
suspension culture
system. Removal of
non-cardiomyocytesthat could induce
adverse effects, suchas arrhythmia andcancer risk.

Highly convenient
productCryopreservableand easy-to-use
cell product. To
be supplied topeople whoneed it when
they need it.

Development of novel cell therapy product utilizing iPIC
To provide the novel treatment option for brittle type 1 diabetes patients, we have established the original
subcutaneous implantation method that supports the long-term engraftment of iPICs even inless-vascularized subcutaneous environments. We have demonstrated proof-of-concept that implanted
iPICs can treat diabetic rodents and pig models. One of the most important features of iPICs is the highpurity of expected endocrine cells, which is achieved by the combinatory approach of single-cell RNA
sequencing-based transcriptomics and unique compound-based purification. Fruitful collaboration withexpertized equipment manufacturers enables us to yield billions of cells from one batch with a cell culture
system optimized for iPICs. Since iPICs are cryo-preservable, the product can be supplied as ready-to-use
within a few days from the frozen iPICs, allowing flexible setting of the implantation date.

To severe chronic
heart failure

Highly efficientengraftable cells
assist cardiac function
for a long period oftime. Continuous
improvement ofcardiac/physicalfunctions will beachieved beyond thecurrent drug therapy.

iPS cells

SolutionwithiPIC

UnlimitedsupplyiPS cell-derived
islet-like cells (iPICs)

Subcutaneous implantation

・Scalable culture
process・Uniformand stable quality
・High purity

・Pancreatic islet-likemorphology
・Physiologicalinsulin secretion・Less invasive andretrievable surgery

Platform Innovation of Orizuru Therapeutics
The benefits from the iPS cell technology, a cutting-edge scientific achievement originating in Japan, havenot been fully offered to the industries, medical institutions, and patients who need it. Through the platform
innovation, Orizuru Therapeutics will support the discovery of innovative pharmaceutical products basedon the iPS cell technology by offering one-stop services to provide a variety of iPS cell- based celldifferentiation/induction technologies, extensive function analysis technologies, and the original versatile
iPS cell platform to be developed in the future in line with the needs of our customers.
We will promote the use of iPS cell technology in society based on the excellent human resources base andthe original iPS cell platform.

To Brittle Type 1 diabetes

・Freedom fromhypoglycemic
events・Independence of
insulin injection
・Minimization of
immunosuppressant use

Solutionsprovidedby platform
innovation

Consolidation ofhuman resources who
inherit the cutting-edge
iPS cell utilization
technology cultivatedat T-CiRA

Production andanalysis technologies
for a wide variety of iPS
cell-derived cells andtissue organoids

Support for drug
discovery researchutilizing iPS cell
technology anddevelopment ofregenerative medicine
research platforms