March 25, 2024
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

Notice of Transfer of EU Orphan Designations of Brincidofovir
TOKYO, Japan, March 25, 2024 – SymBio Pharmaceuticals Limited (Headquarters: Tokyo, “SymBio”)
today announced that orphan designations of brincidofovir for the treatment of adenovirus infection
in immunocompromised patients and prevention of cytomegalovirus disease in the European Union(EU), have been transferred from Emergent Operations Ireland Limited to SymBio Pharma Ireland
Limited (Headquarters: Dublin, Ireland), a subsidiary of SymBio.
Following the completion of the ongoing Phase II clinical trial for adenovirus infection after
hematopoietic stem cell transplantation in the US, SymBio will begin preparations for a Phase III
clinical trial after meeting with the regulatory authorities in Europe, the US, Japan, and the UK. The
Phase III clinical trials are planned to be conducted in four regions (Europe, the US, Japan, and theUK). Authorized orphan medicines benefit from 10 years of protection from market competition once
they are approved.
Orphan designation in the EU (by the European Medicines Agency (EMA)) requires, among otherthings, that the number of patients in the EU is five or less per 10,000 population and that thedisease is life-threatening or chronically debilitating.

SymBio Pharma Ireland Limited (summary)
Name

SymBio Pharma Ireland Limited

Location

Dublin, Ireland

Representative

Takaaki Fukushima

Establishment Date

January 9, 2024

Shareholders

A 100% Subsidiary of SymBio Pharmaceuticals Limited

Business Activities

Research and development of pharmaceuticals and medical devices[Contact]Investor Relations
Tel: +81 (0)3 5472 11251(Note)
About the anti-viral drug Brincidofovir
Brincidofovir (BCV) has a new mechanism of action as a lipid conjugate of cidofovir (CDV). CDV is anantiviral drug already approved and marketed in the United States, but unapproved in Japan. BCV isexpected to be an effective treatment against a wide spectrum of dsDNA virus infections(cytomegalovirus, adenovirus, Epstein-Barr virus, herpes virus, BK virus, papillomavirus andsmallpox virus including monkeypox, etc.), with superior features such as high activity antiviral effectin comparison with CDV and other antiviral drugs. Due to the breakthrough nature of the BCV
molecule, in which a specific length of lipid chain is attached to the CDV, BCV is converted into a
molecule that acts directly within the cell, thereby dramatically increasing the efficiency of cellular
uptake and showing a high antiviral activity. In September 2019, SymBio entered into a license
agreement with Chimerix for the exclusive worldwide rights to develop, market, and manufacture
BCV for all diseases except orthopoxviruses (such as smallpox and monkeypox). The tablets and oralsuspension (oral formulation) were approved on June 4, 2021, for the treatment of smallpox in adults
and pediatric patients, including neonates. In addition to its high antiviral activity, BCV is also
expected to have anti-tumor effects. We are currently conducting collaborative studies with theNational Cancer Centre Singapore, the University of California, San Francisco, and other institutions
to confirm its anti-cancer activity and to identify synergistic effects when combined with its antiviralactivity.
Clinical trials and important R&D collaborations with prominent research institutions include:- Initiated a Phase II clinical trial in patients with adenovirus infection after hematopoietic stem celltransplantation (March 2021) and received Fast Track designation from the FDA (April 2021). Proofof Concept (POC) of antiviral efficacy established based on data up to cohort 3 (May 2023).
- Initiated a non-clinical trial at the University of California, San Francisco Neurosurgery Brain
Tumor Center to evaluate the anti-tumor effect of BCV on refractory brain tumors (September 2021).
- In recent years, numerous studies have demonstrated that EBV is a risk factor for MS. SymBio
entered into CRADA with the NINDS in March 2023 to establish a new antiviral treatment methodfor MS and has been conducting collaborative research to develop a clinical trial.
- CRADA with the National Institute of Allergy and Infectious Diseases (NIAID), affiliated with the 3NIH, to evaluate the efficacy of BCV for EB virus-associated lymphoproliferative diseases (April2023).
- Research on the involvement of infection by reactivation of latent viruses in various neurologicalseverity diseases of the brain, including Alzheimer's disease, has been ongoing for the past several
years, and a simple three-dimensional mimicry of human neural stem cell cultures and brain tissue
established by Tufts University in the United States, the A Sponsored Research Agreement wassigned (December 2022) to examine the effect of BCV on HSV infection using a herpes simplex virus(HSV) infection/reactivation model established by Tufts University in the U.S., which uses humanneural stem cells cultured to mimic brain tissue in three dimensions.

2About SymBio Pharmaceuticals Limited
SymBio Pharmaceuticals Limited was established in March 2005 by Fuminori Yoshida who previouslyserved concurrently as Corporate VP of Amgen Inc. and founding President of Amgen Japan. In May
2016, the Company incorporated its wholly-owned subsidiary in the U.S., SymBio Pharma USA, Inc.
(Headquarters: Durham, North Carolina, Representative: Stephane Berthier).
The Company’s underlying corporate mission is to “deliver hope to patients in need” as it aspires to bea leading global specialty biopharmaceutical company dedicated to addressing underserved medicalneeds.

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