December 19, 2022
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

SymBio enters into Sponsored Research Agreement for non-clinical study to verify theeffectiveness of brincidofovir in a virus-infected brain tissue model

TOKYO, Japan, December 19, 2022 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo,"SymBio" or the “Company”) today announced that the Company has entered into a Sponsored ResearchAgreement (SRA) with Tufts University ("Tufts University") to conduct joint research on theintravenous formulation of the anti-viral drug brincidofovir*1 ("BCV IV"). This joint research is a nonclinical study (the "Study") that will evaluate the efficacy of BCV in a herpes simplex virus (HSV)
infection model using a 3D (three-dimensional) brain model*2 established by Tufts University.
Some double-stranded DNA viruses*3 (dsDNA), such as HSV1, VZV, and HHV6, are directed against
cranial nerve tissues and are known to cause serious diseases in various cranial nerve areas due toinfection caused by their reactivation. BCV is an antiviral drug effective against a broad spectrum ofdsDNA viruses. SymBio is currently conducting global Phase II clinical studies using BCV in patientswith adenovirus infection after hematopoietic stem cell transplantation, and in patients with BK virus
infection after renal transplantation. The research conducted under the SRA will test the potential
utility of BCV against HSV infection and reactivation using human-induced neural stem cells in athree-dimensional bioengineered brain model, which has been established at Tufts University.
Statement from David Kaplan, Chair, Professor of the Department of Biomedical Engineering, Tufts
University and lead investigator with Dana Cairns (research associate in the lab) of the Study: “Thegoal of this study is to provide evidence to support the development of new treatments for neurologicaldiseases for which there is still no fundamental cure."
Statement from Mr. Fuminori Yoshida, President and CEO of SymBio: "In the past few years, Professor
Ruth Itzhaki of Oxford University in the UK has shown that the presence of HSV1 in the brain, incombination with a specific gene, APOE4, increases the likelihood of developing Alzheimer's disease,and there is increasing evidence that dsDNA viruses are involved in neurological disorders, including
Alzheimer's disease. If we can suppress the onset and progression of these diseases by directly
inhibiting the causative virus, we expect to be able to develop therapeutic methods and provide newtreatment options.”

1

The Company does not expect the information presented herein to have any material impact on its
financial outlook for the fiscal year ending December 2022.
[Contact]
Investor Relations
Tel: +81 (0)3 5472 1125
(Note1) About the Anti-viral Drug BrincidofovirBrincidofovir (BCV) is a lipid conjugate of cidofovir (CDV). CDV is an antiviral drug already approved
and marketed in the United States and the European Union, but unapproved in Japan. As BCV exhibits
not only higher anti-viral activity, but also a superior characteristics profile in comparison with CDV
and other antiviral drugs, BCV is expected to be an effective treatment against a wide spectrum ofdsDNA viruses such as herpesviruses, cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus(EBV), papillomavirus and BK virus. Moreover, BCV is expected to be a highly active anti-multiviral
agent that can reduce the risk of nephrotoxicity or myelosuppression, which are serious side effects ofother antiviral drugs including CDV. SymBio entered into an exclusive global license agreement withChimerix Inc. (Headquarters: Durham, NC, "Chimerix") for brincidofovir (BCV) on September 30, 2019.
Under the terms of the agreement, Chimerix grants SymBio exclusive worldwide rights to develop,
manufacture, and commercialize BCV in all human indications, excluding the prevention andtreatment of orthopox infections (which includes smallpox and monkeypox).
The Company aims to expand its business to become a global specialty pharmaceutical company by2030. To maximize business value, the Company is currently conducting a global Phase II clinical trial
mainly in the U.S. for patients with adenovirus infection after hematopoietic stem cell transplantation,and initiated a global Phase II clinical trial mainly in Australia, Japan, and South Korea for patientswith BK virus infection after kidney transplantation in June 2022.
In addition to its high antiviral activity, BCV is also expected to have anti-tumor effects, and we are
currently conducting joint research with the National Cancer Center of Singapore, the University ofCalifornia, San Francisco, and Brown University in the U.S. to confirm BCV’s anti-cancer activity andsynergistic effects when combined with its antiviral activity. Furthermore, the Company has initiateda study to evaluate the potential antiviral activity of BCV against Epstein-Barr virus in collaboration
with the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes ofHealth (NIH) in the U.S.
(Note 2) Herpes simplex virus (HSV) infection model using a 3D (three-dimensional) brain model
Using a porous silk protein sponge with a collagen filler as a substrate, human neural stem cells arecultured in this experimental system where they grow and differentiate into a functional network ofneurons and glial cells, which is sensitive to viral infection. The system can be evaluated for2

electrophysiological function. amyloid ꞵ fiber formation, neuroinflammation, etc. induced by HSV
infection under conditions that exclude other factors.
https://www.science.org/doi/10.1126/sciadv.aay8828(Note 3) Double-stranded DNA (dsDNA) viruses
Double-stranded DNA (dsDNA) viruses includes Herpesviridae (e.g., CMV, HHV-6), adenoviridae(AdVs), polyomaviridae (e.g., BK virus and JC virus), papillomaviridae (HPVs), and poxviridae.

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, President: Carolyn Yanavich).
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.

3