Borofalan (10B)

We are pleased to announce that today we submitted the application to the Ministry of Health, Labour and Welfare (MHLW) to expand the approved use of Borofalan (10B) (development code: SPM‑011, hereinafter “the Drug”), a drug used in BNCT (Boron Neutron Capture Therapy) to treat angiosarcoma. The application is based on the positive results obtained in a domestic Phase II clinical trial of BNCT conducted in collaboration with CICS Corporation for patients with unresectable cutaneous angiosarcoma. In this trial patients with locally advanced or locally recurrent disease for whom chemoradiotherapy or radiotherapy was difficult were enrolled. The study was designed as a single‑arm trial*1 with 10 patients, with the primary endpoint defined as the objective response rate (ORR; complete response (CR) + partial response (PR)) assessed by independent central imaging review*2 within 90 days after BNCT administration. Among the 10 patients who received BNCT, partial responses were observed in 3 patients and complete responses in 2 patients, resulting in an ORR of 50.0% (90% confidence interval*³: 22.2%–77.8%). As the lower limit of the 90% confidence interval met the predefined success criterion established at the time of study planning, the study successfully achieved its primary endpoint. Progression‑free survival*⁴ was defined as the time from BNCT administration to the first confirmation of disease progression or death. The median progression‑free survival was 6.3 months (95% confidence interval: 0.6–not estimable). In addition, no serious adverse drug reactions were observed, and no new safety concerns emerged. Based on these results, the efficacy and safety of the Drug were demonstrated, suggesting that BNCT has the potential to serve as a promising new treatment option for patients with unresectable cutaneous angiosarcoma. Angiosarcoma is an extremely rare malignant tumor classified as a vascular tumor within the group of soft tissue sarcomas. It can arise in various parts of the body, with the skin being the most common site of occurrence, particularly on the scalp of elderly individuals. The disease progresses rapidly, and its prognosis is poor, with a five‑year survival rate of approximately 10%. Currently, when chemoradiotherapy or radiotherapy is difficult to administer, no established treatment options exist that provide effective local control, and there is a strong need for new therapies capable of achieving higher local control rates. According to statistics from the Rare Cancer Center of the National Cancer Center, the estimated number of angiosarcoma patients in Japan is approximately 390 per year, and the disease is classified as a rare disease. Given this situation, the Drug was designated as an orphan drug by the MHLW in December 2023 for the treatment of unresectable cutaneous angiosarcoma. The orphan drug designation is a system designed to promote the research and development of treatments for rare diseases affecting fewer than 50,000 patients in Japan. Under this designation, the Drug has been granted various incentives, including eligibility for government research funding. In addition, orphan drug designation allows the product to undergo priority review during the regulatory approval process, enabling a shorter review period compared with standard pharmaceuticals. We remain committed to making BNCT available as a new treatment option for patients suffering from cancer as soon as possible, and we will continue to advance our efforts toward this goal. *1 Single-arm trial A single-arm trial is a clinical trial in which all participants are treated with the same treatment without dividing them into multiple groups for comparison. *2 Central Imaging Review In pharmaceutical clinical trials, central imaging review refers to a method of evaluating efficacy and safety through an independent review organization (central review body), to ensure objectivity and consistency in image assessments. *3 Confidence Interval A statistical range within which the true value of a measured effect is expected to lie with a given level of confidence (e.g. 90% CI: 22.2–77.8%). *4 Progression-free survival Progression-free survival is one indicator to measure the effectiveness of cancer treatment. It shows the period after treatment until progression or recurrence of cancer, or the time until the death of the patient.

We are pleased to announce that we submitted today the application to the Ministry of Health, Labour and Welfare (MHLW) to expand the approved use of Borofalan (10B) (development code: SPM-011; hereinafter “the Product”), a drug used in BNCT (Boron Neutron Capture Therapy) to treat recurrent meningioma. 　The application is based on the positive results from a physician initiated*1 Phase II randomized controlled trial*2 conducted at Osaka Medical and Pharmaceutical University. 　In this study, the primary endpoint – progression free survival (PFS)*3 as assessed by an independent review committee – was 14.4 months (95% CI: 7.9–26.4) in the BNCT treatment arm, compared with 1.4 months (95% CI: 1.0–9.0) in the control arm receiving the best physician selected available treatment. This difference was statistically significant (p = 0.0157, log rank test). 　Regarding the secondary endpoint of objective response rate (ORR; complete response (CR) + partial response (PR)), a response rate of 27.3% was observed in the BNCT treatment arm, whereas no responses were observed in the control arm. Furthermore, overall survival data demonstrated favorable outcomes in the BNCT arm, with a 1‑year survival rate of 100% and a 2‑year survival rate of 90.9%, supporting the efficacy and safety of the Product. 　The meninges are thin layers of tissue that protect the brain and spinal cord, and meningioma is a type of brain tumor that arises from one of these inner layers. While meningiomas are often benign (WHO Grade 1), high grade meningiomas (WHO Grades 2 and 3) can infiltrate deeply into the brain, cerebral vasculature, and skull, and are prone to repeated recurrence. In some cases, metastasis to other organs such as the lungs may also occur. 　For recurrent disease, surgical resection and external‑beam X‑ray radiotherapy are typically employed; however, their therapeutic effectiveness is limited. In Japan, no pharmaceutical products are currently approved for the treatment of meningioma, and no effective standard therapy has been established. 　According to estimates based on the Ministry of Health, Labour and Welfare’s “Regional Cancer Registry” (2005–2008) and the “Japan Brain Tumor Registry,” the annual incidence of cancers of the brain and central nervous system is approximately 5,000 cases, of which meningiomas account for about 23.8%. This corresponds to an estimated 1,200 new cases of meningioma per year. The “National Cancer Registry” (2021) similarly reports 5,741 cases of brain and central nervous system cancers, supporting the validity of these estimates. Furthermore, based on the Ministry’s “Patient Survey 2023,” the total number of patients living with meningioma (prevalence) in Japan is estimated to be fewer than 23,500. 　In this context, the Product received Orphan Drug designation from the MHLW in September 2024 for the treatment of recurrent meningioma, a condition affecting fewer than 50,000 patients in Japan. This designation, which aims to promote the research and development of therapies for rare diseases, granted various incentives, including eligibility for government research funding support. Furthermore, in February 2026, the Company received an assessment report from the Pharmaceuticals and Medical Devices Agency (PMDA) indicating that the Product qualifies as a priority review item under the Orphan Drug framework. Based on this determination, the Product is expected to undergo a shortened review period compared with a standard application. *1 Investigator-initiated trial An investigator-initiated trial is a clinical trial conducted by a physician who plans and designs the clinical trial for the purpose of obtaining approval for the manufacture and sale of a drug, submits a clinical trial plan notification, and then conducts the trial. The obtained clinical data is passed on to the pharmaceutical company that provided the investigational drug and used in the drug’s regulatory approval application. This trial was conducted with support from the Japan Agency for Medical Research and Development (AMED), a national research and development agency. *2 Randomized controlled trial In a randomized controlled trial, the participants are divided at random into at least two groups. One group is treated with the conventional treatment, and the other group is treated with the new therapy, and the effects of the treatments are verified by observing and comparing the health conditions of the subjects after the treatment. *3 Progression-free survival Progression-free survival is one indicator to measure the effectiveness of cancer treatment. It shows the period after treatment until progression or recurrence of cancer, or the time until the death of the patient.