June 12, 2023
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

Presentation of the Results of Biomarker ResearchPredicting the Antitumor Effects of Brincidofovir at the 17th ICML.
TOKYO, Japan, June 12, 2023 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo, “SymBio” or
the “Company”) today announced that results of its research collaboration with the National Cancer
Centre of Singapore (“NCCS”) on brincidofovir (“BCV”) will be presented by Dr. Jason Yongsheng Chanat the 17th International Conference on Malignant Lymphoma (“ICML”) in Lugano, Switzerland, to beheld from June 13 to 17, 2023.
The highlights of the presentation will include:- In testing NK/T-cell lymphoma cell-lines with both high sensitivity and low sensitivity to BCV, thecell-lines with high sensitivity to BCV correlated well with low expression of TLE1, which acts as atumor suppressor.
- Low expression of TLE1 was also highly correlated with poorer prognosis (PFS: progression-freesurvival) in NK/T-lymphoma patients.
- Low expression of TLE1 was found to be highly correlated with increased expression of MYC and othergenes known as oncogenes.
Statement from Dr. Jason Yongsheng Chan, Principal Investigator of the study, Consultant in theDivision of Medical Oncology, NCCS, and Clinical Assistant Professor at Duke-NUS Medical School:“In this joint research, biomarkers were found in NK/T-cell lymphoma cell-lines that could predict theanti-tumor effect of BCV and are also associated with poor prognosis in patients, which will be very
useful in the development of a new treatment option. The validation of these findings is expected tolead to significant advances in the treatment of hematologic and other malignancies.”
Statement from Mr. Fuminori Yoshida, President and CEO: "The findings of the collaborative study
with NCCS about high correlation between TLE1 and NK/T-cell lymphoma with poor prognosis suggestthat the efficacy of BCV as a new treatment for not only hematologic malignancies but othermalignancies with poor prognosis can be predicted in advance."1

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Tel: +81 (0)3 5472 1125
(Note)
International Conference on Malignant Lymphoma (ICML)The International Conference on Malignant Lymphoma (ICML) is a key event for the scientificcommunity engaged in the study and treatment of lymphoid neoplasms. Organized by the Foundation
for the Institute of Oncology Research (IOR), in cooperation with the American Association for Cancer
Research (AACR) and in collaboration with the European School of Oncology (ESO), the ICML is held
in Lugano (Switzerland) every two years and brings together up to 3,500 physicians and scientists fromall over the world.
National Cancer Centre Singapore (NCCS)
The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre
with specialists who are experts in treating cancer. NCCS attends to the majority of cancer cases in
Singapore’s public healthcare sector.
For further information, please visit NCCS's website: https://www.nccs.com.sg/NK/T-Cell Lymphoma
A type of malignant lymphoma that originates from NK or T cells. NK/T-cell lymphomas are classified
as low grade (progressing yearly), intermediate grade (progressing monthly), or high grade (progressingweekly), and mainly present as extranodal NK/T-cell lymphomas in the perinasal space or on the skin.
This disease is characterized by its relatively high prevalence in Southeast Asia, including China.
MYC
Also known as c-Myc, is one of the oldest oncogenes, and abnormalities of this family of genes have beenfound in a wide range of cancer types, including translocations, mutations, and amplifications inhematopoietic tumors. It functions as a nuclear transcriptional regulator and is known to be a very
important factor in controlling the balance of proliferation and differentiation of hematopoietic cells byregulating the expression of dominant genes.
TLE1
TLE1 is a transcriptional repressor known for its ability to suppress cancer, including hematopoietictumors, by regulating gene expression; low expression of TLE1 has been reported to be associated withpoor prognosis in several cancer types. TLE1 has also been reported to suppress Myc expression andother cancer-promoting signaling pathways.
Biomarker2

A biomarker is a substance in a body, such as a protein or gene that can be used as an indicator ofchanges in a disease state or the effectiveness of treatment. Biomarkers are used to investigate thenature of cancer in advance, predict the effectiveness of treatment, and formulate a treatment plan.
(Source: Cancer Information Service, National Cancer Center Japan)
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 and the European Union, but
unapproved in Japan. BCV is expected to be an effective treatment against a wide spectrum of dsDNAvirus infections (cytomegalovirus, adenovirus, Epstein-Barr virus, herpes virus, BK virus,
papillomavirus and smallpox virus including monkeypox, etc.), with superior features such as highactivity antiviral effect in 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 attachedto the CDV, BCV is converted into a molecule that acts directly within the cell, thereby dramaticallyincreasing 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 assmallpox and monkeypox).
The tablets and oral suspension (oral formulation) were approved on June 4, 2021, for the treatment ofsmallpox in adults and pediatric patients, including neonates.
In addition to its high antiviral activity, BCV is also expected to have anti-tumor effects. We arecurrently conducting collaborative studies with the National Cancer Center of Singapore, theUniversity of California, San Francisco, and other institutions to confirm its anti-cancer activity and toidentify synergistic effects when combined with its antiviral activity.
Clinical trials and major R&D collaborations with prominent research institutions are underway as
follows:- 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). Proof ofConcept (POC) of antiviral efficacy established based on data up to cohort 3 (May 2023).
- Initiated Phase II clinical trial in patients with BK virus infection after renal transplantation (May2022).
- 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).
- With regard to multiple sclerosis, an intractable disease that has recently been proven to be associatedwith the EB virus, the National Institute of Neurological Disorders and Stroke (NINDS), affiliated with
the National Institutes of Health (NIH), will examine BCV's efficacy against the EB virus in the3treatment of multiple sclerosis, and to obtain information needed to conduct future clinical trials(March 2023).
- CRADA with the National Institute of Allergy and Infectious Diseases (NIAID), affiliated with theNIH, to evaluate 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 was signed(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 human neural 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, 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.

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