November 15, 2022
Metcela Inc.

Metcela Eligible to Receive up to $7 Million (1Billion JPY) AMED Grant for Promoting theDevelopment of Regenerative Medicine Product
Using Cardiac Stem Cells
Accelerate the Phase III clinical trial of cardiac stem cell-based product forpediatric congenital heart disease patients

Kanagawa, Japan - Metcela Inc. has been selected by the Japan Agency for
Medical Research and Development ("AMED") for the start-up type of theCyclic Innovation for Clinical Empowerment (CiCLE) called ViCLE.

■About the selected project
The project will focus on the development of JRM-001, autologous cardiac stem
cell-based product, for pediatric congenital heart disease patients and proceed with
the Phase III validation study to confirm its efficacy and safety through collaboration
with Okayama University. With this selection Metcela will be eligible to receive up to1 billion JPY in contract funding for up to 5 years.
JRM-001 is subject to the Japanese Ministry of Health, Labor and Welfare’s
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SAKIGAKE Designation, and is expected to be launched as a breakthroughtreatment for rare diseases in children.

■About JRM-001
Targeting single ventricle and its challenges
Single ventricle is a rare congenital heart disease in which the heart has only one
functioning ventricle to pump blood, and it affects about 310 to 810 people per year
in Japani. Although series of anatomical repair surgery is performed as a standardof care and the postoperative survival rate has been improving in recent years, 90%of postoperative patients will develop cardiac dysfunction or heart failure by the ageof 40. The 20-year survival rate is about 69%, making it a disease with a poor
prognosisii. With repeated surgical procedures starting in early childhood and thediseases’ impact on the growth and employment in adulthood, these patients often
experience reduced quality of lifeiii. Despite these debilitating impacts, no drugs orregenerative medicine products that are indicated to have cardiac functional
improvement have been approved to date.
Treatment concept
JRM-001 is aregenerative medical
products that is mainly
consisted of cardiac
stem cells (CSCs).
During standard of caresurgery, a small piececardiac tissue is biopsiedand used as the starting
material for JRM-001. The tissues are then transported to a cell processing facility
and they are cultured and formulated. The final product is transported back to themedical facility and administered back into the patient's heart during routine
cardiac catheter examination (Figure).
As an autologous product, JRM-001 is characterized by minimal burden on
patients and low risk of immune rejection.

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Development results to date
Metcela acquired Japan Regenerative Medicine Co., Ltd. (JRM) in April 2022 andsucceeded the development of JRM-001. Research results suggesting the safety andefficacy of the treatment using CSCs for single ventricle have been established inthe Phase Iiv and Phase IIv clinical studies conducted by Okayama University. Basedon these results, Phase III validation study was initiated.

■Comments from the development teamDr. Shingo Kasahara
Professor and Director, Department of Cardiovascular Surgery, Okayama
UniversityDirector, Department of Pediatric Cardiovascular Surgery
The project selected focuses on the development of regenerative medicine productto treat a congenital heart disease called single ventricle.
The development of various surgical procedures has improved the prognosis forpatients with single ventricle. However, the major issue is that some of the patients
suffer from severe heart failure due to the loss of function of the cardiac muscle, acommon characteristic of single ventricle. This severe heart failure also causes a
chain reaction of multiple organ dysfunction and failure throughout the body.
Through two clinical studies conducted to date, Okayama University has confirmed
the long-term efficacy of cardiac stem cells. With this project, we hope to complete
the Phase 3 validation study together with Metcela and bring this innovative
treatment to patients as soon as possible.
Kohtaro Toda, Vice President of Japan Regenerative Medicine Division,Metcela Inc.
Japan Regenerative Medicine Co., Ltd. was founded in 2013, and since then, we
have consistently worked on the development of JRM-001 with a strong sense ofmission to bring a new therapeutic product to children in need. Upon merger with
Metcela, we have succeeded in resolving various technical issues in a short periodof time.
We are strongly convinced that the practical application of this technology will leadto hopes for patients with single ventricle, for whom treatment options are limited.

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■Outline of Accepted Project1.

Project title: Development of a treatment for pediatric patients withcongenital heart disease using cardiac stem cells

2.

R&D organization
Representative Organization: Metcela Inc.
Organization: Okayama University

3.

Grant period and total contracted cost: up to 5 years, maximum 1 billion yen

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Reference: https://www.amed.go.jp/koubo/17/01/1701C_00002.html■About Metcela
Metcela Inc., established in 2016, is a clinical-stage biotechnology startup
pioneering the research and development of fibroblast and stem cell-based therapy
for chronic diseases that currently have limited therapeutic options. MTC001 is acombination product of autologous cardiac cells (VCAM-1-positive Cardiac Fibroblast,VCF) and a novel catheter delivery system targeting chronic heart failure patients.
MTC001 offers two major advantages over other cell therapies: (1) the therapeutic
cells are autologous (patient-derived) and homologous (tissue-specific i.e. cardiacderived), which is most suitable for the heart, as it is a highly immunogenic organ,and (2) the minimally invasive catheter system is equipped with a highly functional
injection needle specifically designed for this therapy to achieve reliable and safeadministration of the cells.
Website: https://www.metcela.com/en/i

Our estimate from the Intractable Disease Information Center, description of the disease:https://www.nanbyou.or.jp/entry/4369

ii

Intractable Disease Information Center, overview, diagnostic criteria, etc.:
https://www.nanbyou.or.jp/entry/4370

iii

The concept of quality of life.

iv

Ishigami et al. Circ Res. 2015 Feb 13;116(4):653-664v

Ishigami et al. Circ Res. 2017 Mar 31;120(7):1162-1173, Sano et al. Circ Res. 2018 Mar 30;122(7):9941005

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