July 12, 2024
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

SymBio Pharmaceuticals Announces Publication of Research Showing Antiviral Drug
Brincidofovir Inhibits Infectious Viral Production of Polyomavirus
TOKYO, Japan, July 12, 2024 – SymBio Pharmaceuticals Limited (Headquarters: Tokyo, “SymBio”
or the “Company") today announced that Penn State College of Medicine (Pennsylvania, UnitedStates) has published the results of preclinical research showing the antiviral activity of brincidofovir("BCV") against polyomavirus.
In November 2022, SymBio entered into Material Transfer Agreement (MTA)1 with Penn State
College of Medicine (Professor Aron Lukacher) to evaluate the potential usefulness of BCV in a mousemodel infected with polyomavirus. SymBio is pleased to announce that new findings from theresearch have been published by Professor Lukacher in the journal mBio®.
Highlights of the published findings include:
Primary culture in vitro test using mouse kidney cells and brain cortical cells:•BCV inhibited virus production after Murine Polyomavirus (MuPyV) infection•Findings suggest that the suppression of infectious virus production involves a reduction ofviral T antigen2

In vivo studies in mouse models:•BCV suppresses infectious virus production in kidney and brain from relatively low doses•

Preventive and therapeutic effects on chronic infection in an immunodeficient mouse modelStatement from Professor Aron Lukacher: “I am very pleased that our study provides new insights
into an antiviral agent that may be of great benefit to patients suffering from life-threatening
diseases caused by polyomaviruses.”
Statement from Fuminori Yoshida, President and CEO: “There are no drugs approved for severepolyomavirus infection, and effective agents are desperately needed. We will be working withProfessor Lukacher on further studies to validate the anti-polyomavirus activity of BCV.”[Contact] Investor Relations / Tel: +81 (0)3 5472 1125
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1. Related news releases:
24 November 2022: SymBio enters into Material Transfer Agreement with Penn State College ofMedicine for a non-clinical study to evaluate the efficacy of brincidofovir in a polyomavirus model
2. T antigen:T antigen is a viral protein required for polyomavirus replication and virus production.
3. Mouse model of polyomavirus virus infection
Polyomavirus infections such as BK virus and JC viruses are asymptomatic in healthy individuals
where they persist mainly in the urinary tract and lymphoid tissues. However, when the body's
immune system is compromised, these viruses reactivate and can cause severe infections in thekidney, bladder, and brain. There are no antiviral drugs against polyomaviruses, and there are few
preclinical models for these viruses that infect only humans. The model established in Prof.
Lukacher's lab represents polyomavirus infection in mice using murine polyomavirus which has agenome structure and mode of infection similar to that of the human polyomaviruses. This mousemodel allows us to examine the involvement of immune mechanisms as well as infection in the kidneyand central nervous system.
Information of the Published Articles:
Butic AB, Katz ZE, Jin G, Fukushima K, Hazama M, Lukacher AE, Lauver MD. 2024. Brincidofovir
inhibits polyomavirus infection in vivo. mBio e0104924.
https://doi.org/10.1128/mbio.01049-24
About the antiviral 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 (EBV), 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 amolecule 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 also2

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 2a 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 Phase 2a clinical trial in patients with CMV infection after Hematopoietic Stem Cell
Transplantation in June 2024.
- 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).
- A number of recent studies have demonstrated that EBV is a risk factor for MS. SymBio entered into
CRADA with the NINDS at the NIH in March 2023 to establish a new antiviral treatment method for
MS and has been conducting collaborative research to develop a clinical trial.
- CRADA with the National Institute of Allergy and Infectious Diseases (NIAID) at the NIH toevaluate the efficacy of BCV for EB virus-associated lymphoproliferative diseases (April 2023).
- 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.
About SymBio Pharmaceuticals Limited
SymBio Pharmaceuticals Limited was established in March 2005 by Fuminori Yoshida who previously
served 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: John Houghton).
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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