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 andthe 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 is initially focused on two potential therapies researched under the T-CiRA program. One iswith iPS cell-derived cardiomyocytes led by Project Leader Yoshinori Yoshida (Associate Professor at CiRA)
and the other is with iPS cell-derived pancreatic islet cells led by Project Leader Taro Toyoda (Junior
Associate Professor at CiRA). We will continue to seek other potential therapy where iPS cell technology
may play a critical role. Another business scope is to support any drug discovery research activities and tobuild 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 inyoung, open, and free, yet our heart is "to help society and patients per iPS cell technologies come fromJapan." 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 atShonan iPark campus, Kanagawa, Japan. By providing regenerative medicines, we will contribute to thefuture 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 at Shonan
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 the Shin-Shonan
Bypass via Fujisawa-Bashi

1Shonan 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 with iPS cell-derived pancreatic islet cells (iPICs)
to brittle Type 1 diabetes patients as a replacement therapy for islet transplantation.

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

What is Platform InnovationiCM is an 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 by small molecule compound discovered in the T-CiRA program. By transplanting iCMs, considered
to be highly engraftable, pure, and safe cardiomyocytes, into the patient's heart, they are expected toreplenish the cardiomyocytes lost as the disease progresses and promote remuscularization. Restoring thecardiac function of patients with severe heart failure, which has been considered difficult to treat, can beexpected to improve 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 at CiRA.
iPIC is an aggregate of high-purity pancreatic endocrine cells that contains both insulin and NKX6.1 positivecells, a characteristic of pancreatic β cells. After implantation in vivo, pancreatic islet-like structurescontaining glucagon positive cells, another important endocrine cell type, are formed, and physiologicalinsulin-secreting capabilities can be demonstrated in response to glucose loading and hypoglycemia.

By utilizing the cutting-edge iPS cell and its related technologies that have been cultivated through theT-CiRA program, we will support the creation of innovative pharmaceutical products through new drug
discovery approaches and develop infrastructures for regenerative medicine research to provide iPS cell
products at a reasonable cost and stable supply.

iPIC before implantation

iPIC after implantation

Human cadaveric
pancreatic islets

Maturationin vivo

Development of novel cell therapy product utilizing iPIC

Our strength
Cardiomyocyte therapy requires the delivery of hundreds of millions of cardiomyocytes or more to patients.
To provide cell products to patients with severe heart failure who are awaiting treatment, it is necessary todevelop cell manufacturing technologies that can efficiently produce large numbers of cells. One of themost important technologies is a culture technique in which cells are suspended in a medium and 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 high-quality
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 are highlyeffective when administered as single cells, eliminating the need for sheet or aggregate reformation. Inaddition, iCM is suitable for a wide range of administration methods, including catheter administration,
enabling minimally invasive treatment with less burden on the patient.

SolutionwithiCM

Achievement of both highproductivity and high purity.
Mass production-friendly
suspension culture system.
Removal of
non-cardiomyocytes that could
induce adverse effects, such as
arrhythmia and cancer risk.

Stable supply to thepeople who need it
when they need it.
Cryopreservable andoff-the-shelf cell
product

Assisting cardiac
function for a long
period of time.
High efficacy can beachieved with our highly
efficient engraftablecardiomyocytes beyond
the current drug therapy.

To provide the novel treatment option to brittle Type 1 diabetes patients, we have established the original
subcutaneous implantation method that supports the long-term engraftment of iPIC. So far, we havedemonstrated proof-of-concept that implanted iPIC can treat diabetic rodents and pig models. High purityof expected endocrine cells, achieved by the combinatory approach of single-cell RNA sequencing-basedtranscriptomics and original compound-based purification, is one strength of our product. Fruitfulcollaboration with expertized equipment manufacturers enables us to yield billions of cells from one batchwith a cell culture system optimized for iPIC. Now we are developing a product that can be supplied with thefreeze-thaw tolerable iPIC for immediate use.

iPS cells

SolutionwithiPIC

UnlimitedsupplyiPS cell-derived
islet-like cells (iPICs)

Subcutaneous implantation

・Scalable culture
process・Homogeneousand stable quality
・High purity

Background of the Orizuru Therapeutics and T-CiRA

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

The discovery of induced pluripotent stem cells (iPS cells) in 2006 had a strong influence on thedevelopment of stem cell research and opened the infinite possibilities for drug discovery andregenerative medicine.
To develop clinical applications of iPS cells, CiRA at Kyoto University and Takeda Pharmaceutical
Company Limited (Takeda) have been conducting the “Takeda-CiRA Joint Program for iPS CellApplications” (T-CiRA) since its agreement in 2015.
As the program progresses, a new framework is required to accelerate the realization of iPS
cell-based therapeutics in a timely and effective manner, and Orizuru Therapeutics was establishedas one such approach. Orizuru Therapeutics will promote technological innovation and utilizationof iPS cells and their related platforms, and contribute to the development of new therapeutic
options.

T-CiRA Joint Research Program

Brittle Type 1 diabetes

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

Solutionsprovidedby iPS cellutilization
technology

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