June 24, 2024
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

Confirmed Antitumor Effects of Brincidofovir in Peripheral T-Cell Lymphoma
Suppression of the oncogenic MYC and Induction of Expression of Immunogenic Response Pathways

TOKYO, Japan, June 24, 2024 – SymBio Pharmaceuticals Limited (Headquarters: Tokyo, “SymBio”
or the “Company") is currently collaborating with the National Cancer Centre Singapore ("NCCS") toevaluate its anti-tumor effects of brincidofovir ("BCV"). The result of the study was presented at theEHA2024 Hybrid Congress held in Madrid, Spain from June 13 to 16, 2024.
Results of our collaborative research with NCCS showing the anti-tumor effect of BCV on NK/T-celllymphomas were reported at the 2022 American Society of Hematology meeting and the 2023
International Conference on Malignant Lymphoma. In this presentation, we report that BCV wasevaluated using human T-cell lymphoma cell lines, including peripheral T-cell lymphoma (PTCL), andxenograft mouse models, and showed similar anti-tumor effects against these lymphomas as against
NK/T-cell lymphomas.
Highlights of the research results presented include:
1) BCV showed high concentration-dependent cytotoxicity in all T-cell lymphoma cell lines
examined.
2) In a xenograft mouse model, intraperitoneally administered BCV significantly and clearly
inhibited tumor growth compared to the control group.
3) Similar changes were observed in BCV-treated PTCL cells in gene expression changes in theNK/T-cell lymphoma model, particularly in gene expression of immunomodulatory functions suchas decreased MYC-related gene expression and increased IFNγ expression, which indicate antitumor effects.
Statement from Fuminori Yoshida, President and CEO: “As we promote the BCV business platform,
the anti-tumor effect was confirmed in PTCL as well as NK/T-cell lymphoma, and we aim to start
clinical trials for NK/T-cell lymphoma and PTCL, which are currently unmet therapeutic areas, assoon as possible. The anti-tumor effect is also expected to be contributed by suppression of Myc
expression and induction of immune-related gene expression, suggesting anti-tumor effects not only1

in hematological malignancies but also in solid tumors.”[Contact]
Investor Relations
Tel: +81 (0)3 5472 1125

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(Note)Peripheral T-cell lymphoma (PTCL)
PTCL is a general term for a variety of lymphoid tumors derived from T cells that have differentiatedand matured in the thymus and migrated to peripheral tissues, and is a rare cancer classified as a
rapidly progressing aggressive lymphoma. PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL),
ALK-positive anaplastic large cell lymphoma (ALCL), and ALK-negative ALCL are the major types.
Primary treatment involves multidrug chemotherapy and radiation, but they are not always effectiveenough. Although various therapeutic agents have been clinically used for relapsed or refractory
PTCL in recent years, no standard treatment has been established, and the development of new
therapeutic agents is desired.
Mouse Xenograft Model
Xenograft models using highly immunocompromised mice have been used to transplant humancancer cell lines for the evaluation of anticancer drugs targeting cancer cells.
European Hematology AssociationThe European Hematology Association holds annual meetings attended by experts from around theworld.
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 (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 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.

3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 BrainTumor 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 in March 2023 to establish a new antiviral treatment method for MS andhas been conducting collaborative research to develop a clinical trial.
- CRADA with the National Institute of Allergy and Infectious Diseases (NIAID), affiliated with the 3
NIH, 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.
About SymBio Pharmaceuticals LimitedSymBio 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: 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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