December 11, 2023
SymBio Pharmaceuticals Limited
Fuminori Yoshida
Representative Director
President and Chief Executive Officer(Securities Code: 4582)

SymBio Presents New Positive Data from Ongoing Phase 2a Study of IV Brincidofovir
in Adenovirus Infection in Oral Presentation
at the 65th American Society of Hematology (ASH) Annual Meeting

TOKYO, Japan, December 11, 2023 -- SymBio Pharmaceuticals Limited (Headquarters: Tokyo, Japan,“SymBio” or the “Company”) today announced that POC data demonstrating the antiviral efficacy ofbrincidofovir from the Company’s ongoing Phase 2a clinical trial of intravenous of brincidofovir (IVBCV) in immunocompromised patients with adenovirus (AdV) infection, was presented in the oral
session at the 65th American Society of Hematology Annual Meeting and Exposition, December 9-12,2023, in San Diego, California, U.S.A. This presentation was given by the lead investigator of the study,
Dr. Michael Grimley, MD, Medical Director, Division of Bone Marrow Transplantation and Immune
Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
In a dose ascending Phase 2a study, a total of 27 immunocompromise patients with AdV viremia,including recipients of allogeneic hematopoietic cell transplant, were treated in 3 cohorts with IV BCV
twice weekly. Treatment with IV BCV at 0.4 mg/kg* demonstrated potent antiviral activity withclearance of AdV viremia in 100% of 10 patients treated. Among 90% of those patients, clearance ofAdV viremia was achieved within 4 weeks of treatment (table 1, graph 1).

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Of the 27 patients treated with IV BCV twice weekly across all cohorts, TRAEs were observed in 7
patients and serious TRAEs including gastrointestinal and hepatic toxicities described with the oral
BCV formulation were not observed. All TRAEs were reversible and resolved after the completion ofthe treatment. Adverse event-related discontinuations were observed in 6 of the 27 patients acrosscohorts, including in one of 10 patients treated with 0.4 mg/kg IV BCV.
*: or 20 mg for patients weighing ≥50 kg

The presentation concluded that in view of promising results and in the absence of any other approved
treatments for AdV infection, the results demonstrate a safe and effective dose of IV BCV for thetreatment of AdV infection and support the progression to Phase 3 clinical trial.

“We are very pleased to announce the oral presentation of data from a Phase 2 study demonstrating
the antiviral efficacy of IV BCV as a treatment for AdV infection. Based on the data from this study,
SymBio is preparing to initiate a Phase 3 study for the approval of BCV in a therapeutic area of highunmet medical need,” commented Fuminori Yoshida, President and CEO.
“Adenovirus remains devastating cause of life-threatening infection in both hematopoietic stem celltransplant (HSCT), solid organ transplant (SOT) and other immune-compromised patients. Whilecurrently no drugs are approved to treat this infection, this data demonstrates that IV BCV is effective
in human against AdV infection. Our team remains committed to continue the development efforts tomeet the regulatory approval,” says Nkechi Azie MD, the global CMO.
Details of the presentation at ASH are as follows:
https://ash.confex.com/ash/2023/webprogram/Paper179901.html
Title: Preliminary Results of a Phase 2a Clinical Trial to Evaluate Safety, Tolerability and Antiviral
Activity of Intravenous Brincidofovir in Immunocompromised Patients with Adenovirus Infection(Abstract #112)
Session Name: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute
Toxicities: Improving Outcomes by Reducing Transplant-Related Complications
Room: San Diego Convention Center, Room 11[Contact]
Investor Relations
Tel: +81 (0)3 5472 1125

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(Note)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 human diseases except orthopoxviruses (suchas smallpox 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 are
currently conducting collaborative studies with the National Cancer Centre Singapore, the Universityof California, San Francisco, and other institutions to confirm its anti-cancer activity and to identify
synergistic effects when combined with its antiviral activity.
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 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 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).
- In recent years, large numbers of 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 forMS, and has been conducting collaborative research to develop a clinical trial.
- 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)3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., called 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 be a leading global
specialty biopharmaceutical company dedicated to addressing underserved medical needs.

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