March 18, 2024
SymBio Pharmaceuticals LimitedFuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

Research results showing anti-proliferative activity of brincidofovirin B-cell lymphoma to be presented at the AACR Annual Meeting 2024
TOKYO, Japan, March 18, 2024 -- 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 at the AACR Annual
Meeting 2024 in San Diego, California, scheduled to be held from April 5 to April 10, 2024.
Highlights of the presentation will include:- The anti-tumor effect of BCV was evaluated using 19 B-cell lymphoma cell lines (diffuse large B-celllymphoma, Burkitt lymphoma and Hodgkin lymphoma) in comparison with NKTCL cell lines. Mouse
xenograft models were deployed to assess in vivo effects.
- BCV inhibited viability in all B-cell lymphoma cell-lines in a dose-dependent manner. (IC500.0798~8.414 µg/ml)- Nine cell lines, including the double-hit DLBCL cell-line, showed marked sensitivity.
(IC50 < 1 µg/ml)- DLBCL patient samples from two independent datasets showed that TLE1-high tumors conferredworse overall survival. These findings are in stark contrast to NKTCL, in which TLE1 loss confers
BCV sensitivity in vitro and is associated with poor survival outcomes in patients.
- These results suggest that BCV may be a potential novel therapeutic agent for the treatment of Bcell lymphomas.
Following the ICML conference presentation on biomarkers in NK/T-cell lymphomas in June 2023, we
conducted a study on the anti-tumor activity of BCV in B-cell lymphomas, including refractory,
double-hit DLBCL, the results of which will be presented at the AACR Annual Meeting 2024.
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Tel: +81 (0)3 5472 1125

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(Note)Presentation Abstract:
https://www.abstractsonline.com/pp8/#!/20272/presentation/8985
Double-hit lymphoma (classified as DLBCL/HGBL with MYC and BCL2 rearrangement in the 5thedition of the WHO classification)
Previously included in high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6
rearrangements, known as lymphomas with very poor prognosis.
Mouse xenograft model
Xenograft models using highly immunocompromised mice are used to transplant human cancer celllines and to evaluate anticancer drugs targeting cancer cells.
AACR Annual Meeting
The AACR Annual Meeting is the focal point of the cancer research community, where scientists,clinicians, other health care professionals, survivors, patients, and advocates gather to share thelatest advances in cancer science and medicine. From population science and prevention; to cancer
biology, translational, and clinical studies; to survivorship and advocacy; the AACR Annual Meeting
highlights the work of the best minds in cancer research from institutions all 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/
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 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 oral

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suspension (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 cell transplantation (March 2021) and received Fast Track designation from the FDA (April2021). Proof of Concept (POC) of antiviral efficacy established based on data up to cohort 3 (May2023). - 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 (September2021). - 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
method for MS and has been conducting collaborative research to develop a clinical trial. - CRADAwith the National Institute of Allergy and Infectious Diseases (NIAID), affiliated with the 3 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 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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