SyB V-1901

Antiviral Drug
Brincidofovir SyB V-1901: Intravenous Formulation

Overview

SyB V-1901 is an intravenous formulation of brincidofovir (“BCV”). BCV is a lipid conjugate of cidofovir (“CDV”, which is CDV is approved in the United States but not in Japan). Once inside the cells, BCV is converted into CDV-PP (CDV diphosphate), the active form of the drug. BCV exhibits significantly more efficient cellular uptake compared to CDV, resulting in higher intracellular concentrations. BCV has a high antiviral effect at lower doses due to the inhibition of viral replication by CDV-PP. BCV also exhibits a broader spectrum of antiviral activity than CDV or other antivirals, and is believed to be effective against a variety of double-stranded DNA viral infections, including cytomegalovirus, herpes viruses such as Epstein-Barr virus (EBV), adenovirus, BK virus, papillomavirus, and smallpox virus and mpox virus. In addition, BCV is not associated with nephrotoxicity and myelosuppression, which are serious side effects of other antiviral drugs, including CDV.
Taking advantage of these characteristics of brincidofovir, SymBio Pharmaceutical is developing products in three therapeutic areas: post-transplant infections, blood cancers and solid tumors, and neurodegenerative diseases.  　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　Leveraging the unique characteristics of brincidofovir, SymBio is developing the drug in three therapeutic areas: post-transplant infectious diseases, hematology and oncology, and neurodegenerative diseases.

Post-transplant Infectious Diseases

Adenovirus

Adenovirus (AdV) infections in immunocompromised patients, such as those who have undergone hematopoietic stem cell transplantation or organ transplantation, are estimated to affect 4,000 patients annually in Japan, the US, and Europe. Therefore, Symbio decided to prioritize the global development of IV BCV. In March 2021, we initiated a Phase IIa clinical trial primarily targeting children (but also adults) with adenovirus infections. Human proof of concept (POC) was established in May 2023 and completed in the first half of 2024. In the global Phase III clinical trial, in addition to major EU countries and the United States, clinical trials have begun in six countries—Austria, Belgium, Denmark, the Netherlands, Portugal, and Sweden—with 41 patients enrolled as of October 22. Case accumulation is progressing smoothly in the target countries and regions. This study plans to enroll 180 patients at a total of 80 sites, mainly in the US and Europe. This development program has already received orphan drug designation in Japan and Europe, approval for a pediatric investigation program (PIP) in Europe, and fast track designation in the United States.

Cytomegalovirus

A Phase IIa clinical trial conducted in the United States for patients with cytomegalovirus infection after hematopoietic stem cell transplantation was presented orally as a Late-Breaking Abstract at the Tandem Meetings held in Utah, USA in February 2026. The study demonstrated a reduction in CMV levels and good tolerability (tolerance to side effects) in patients with multiple prior treatment histories, suggesting the potential of this drug as a new treatment option for CMV-infected patients with limited treatment options. However, development has been temporarily suspended to focus on development for AdV infection.

○Hematology/Oncology

In addition to its high antiviral activity, BCV has also been shown to have anti tumor effects, and we are exploring new indications in the field of solid tumors through collaborative research with research institutions in various countries.

Malignant brain tumors (glioblastoma)

Since 2021, we have been conducting collaborative research with the Brain Tumor Center University of California San Francisco, on the antitumor effects of BCV on brain tumors. The research results have been presented at several international and domestic conferences, and we are currently preparing for the start of a physician-initiated Phase II clinical trial.
Gliomas, brain tumors that originate from glial cells in the brain, progress very rapidly, have a poor prognosis, and a high mortality rate, and currently there is no effective treatment. For grade 4 glioblastoma, the most malignant type, the median survival time after diagnosis is short, ranging from 2 to 18 months, and the 5-year survival rate is less than 5%. Cancers with a 5-year survival rate of less than 50% are classified as "refractory cancers." Glioblastoma, one of these refractory cancers, is estimated to affect approximately 2,300 people annually in Japan and approximately 28,000 people annually in Europe and the United States.

Head and Neck Cancer

It is estimated that 150,000 people worldwide suffer from head and neck cancer. On October 20, 2025, at the European Society for Medical Oncology (ESMO Congress 2025, Berlin, Germany), we presented the results of preclinical study, including a significant combination effect of BCV with an immune checkpoint inhibitor (anti-human PD-1 antibody), regarding the therapeutic effect of BCV on head and neck cancer. We are currently preparing for the start of a physician-initiated Phase II clinical trial.

EB virus-associated gastric cancer

The number of patients with EB virus-associated gastric cancer worldwide is estimated at 13,000.
Preclinical study results showing that combination therapy with BCV and immune checkpoint inhibitors could be a new treatment option for EB virus-related gastric cancer were presented at ASCO (American Society of Clinical Oncology) in June 2026. Preparations are underway to begin investigator-initiated clinical trials.

EB virus-associated lymphoproliferative disorder (LPD)

We extended for three years the Collaborative Research and Development Agreement (CRADA) that we signed in 2023 with the National Institute of Allergy and Infectious Diseases (NIAID), a subsidiary of the National Institutes of Health (NIH), regarding LPD. Having successfully created an animal model involving EBV reactivation using humanized mice, future collaborative research will aim to utilize this animal model to verify the therapeutic effects of BCV and accumulate knowledge in preparation for the start of clinical trials.

Malignant Lymphoma

The international collaborative Phase Ib clinical trial, currently suspended, involving patients with malignant lymphoma, showed a partial response (PR, an indicator of tumor reduction) in one patient with relapsed or refractory malignant lymphoma, suggesting that the anticancer activity of this drug, as confirmed in animal studies, is also present in humans. We believe that this trial has provided valuable insights into the oncology development of IV BCV.

Neurodegenerative Diseases

PML

The polyomavirus JC virus (JCV), a type of double-stranded DNA virus (dsDNA virus), is known to cause PML, a severe demyelinating disease affecting the brain. With an estimated 4,000 patients in Japan, the US, and Europe, this disease is largely ineffective against existing antiviral drugs, making the development of an effective treatment highly anticipated. In February 2026, we signed a CRADA agreement with the National Institute of Neurological Disorders and Stroke (NINDS) within the National Institutes of Health (NIH). Based on this agreement, we have commenced a Phase II clinical trial at the NIH Clinical Center targeting PML, a rare disease caused by the activation of JCV using IV BCV. The first patient enrollment was completed in June 2026, and as of October, enrollment has progressed to 11 cases.

Multiple Sclerosis

Regarding multiple sclerosis (MS)—an intractable disease estimated to affect approximately 3 million people worldwide—a study published in *Science* in January 2022 reported that Epstein-Barr virus (EBV) infection is a major risk factor for the onset of MS and that antiviral drugs could be used to target EBV. In addition, a series of reports on the mechanisms linking EBV infection to the onset of MS were published in *Nature*.
SymBio In March 2023, the pharmaceutical company entered into a CRADA with NINDS and began joint research aimed at developing a novel treatment directly targeting the EBV; the results were published in the *Journal of Clinical Investigation* in January 2026.This strongly suggests the potential for developing a groundbreaking multiple sclerosis treatment that differs from conventional therapies aimed at eliminating B-cell lymphocytes. In March 2026, the CRADA was extended for three years, and we will continue our research with the goal of advancing it to human applications. Furthermore, regarding patents already filed for inventions resulting from research conducted under the CRADA, we entered into a licensing agreement in September with the U.S. Department of Health and Human Services granting us an exclusive license. This license agreement enables our company to exclusively utilize the patents in question should new treatments based on the aforementioned filed patents be commercialized in the future.

Herpes Simplex Virus Type 1 and Alzheimer's Dementia

Some dsDNA viruses, including herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV), have a tendency to target brain and nerve tissue. Increasing research suggests that the reactivation of these latent viruses may be involved in various neurological diseases, including Alzheimer's disease (AD). Based on findings from collaborative research with Tufts University in the United States, SymBio Pharmaceuticals will proceed with the development of BCV for Alzheimer's disease and mild cognitive impairment (MCI). Furthermore, based on research results obtained from preclinical studies conducted in collaboration with academia, we will file patent applications and enter into licensing agreements to exclusively advance future development and commercialization in this disease area.

Other Collaborative Research

Currently, we are promoting collaborative research and development in the fields of viral infections, solid tumors, and neurodegenerative diseases with leading research institutions around the world, including the National Institute of Neurological Disorders and Stroke in the United States and the Gustav Roussy Institute in France. We also actively present the results of our collaborative research at academic conferences. For more details, please refer to the page below.

License

In September 2019, SymBio signed a license agreement with Chimerix, Inc. (Headquarters: North Carolina, USA) to acquire exclusive rights to BCV worldwide, including development, sales and manufacturing, for all diseases except orthopoxviruses (such as smallpox and empox). In September 2022, Emergent Biodefense Operations Lansing LLC, a subsidiary of Emergent BioSolutions Inc., which received the license for BCV from Chimerix, became our licensor.
BCV has also been designated an orphan drug for the prevention of adenovirus and cytomegalovirus infections in immunocompromised patients in the European Union.