Otsuka Pharmaceutical Co., Ltd. (Otsuka) is pleased to announce our entry into an exclusive worldwide licensing agreement with Ionis Pharmaceuticals, Inc. (Ionis) for rights to manufacture and market Ionis' ulefnersen (generic name; development code is ION363), a drug candidate under development for the treatment of patients with amyotrophic lateral sclerosis (ALS) caused by mutation of the fused in sarcoma (FUS) gene.

大冢制药株式会社（大冢）欣然宣布与 Ionis Pharmaceuticals, Inc.（Ionis）达成全球独家许可协议，获得生产和营销 Ionis 的 ulefnersen（通用名；开发代码为 ION363）的权利，该药物是一种正在开发中的候选药物，用于治疗因融合肉瘤( FUS) 基因突变引起的肌萎缩侧索硬化症 (ALS) 患者。

This agreement marks Otsuka's second introduction of an antisense oligonucleotide (ASO) medicine from Ionis, following our acquisition of development and sales rights in Europe and Asia, including Japan, for the hereditary angioedema attack suppressant drug donidalorsen (generic name).

此项协议标志着大冢公司第二次从 Ionis 引进反义寡核苷酸 (ASO) 药物，此前我们收购了遗传性血管性水肿发作抑制剂 donidalorsen（通用名）在欧洲和日本等亚洲的开发和销售权。

ALS is a serious neurodegenerative disease that causes rapid muscle weakness in the limbs and respiratory muscle paralysis. Once the disease has manifested, it generally continues to progress, and in a few years it can become difficult to breathe spontaneously. The number of ALS patients worldwide is on the rise, and it is estimated that by 2040 there will be over 300,000 people with the disease.

ALS 是一种严重的神经退行性疾病，会导致四肢肌肉迅速无力、呼吸肌麻痹。一旦发病，病情通常会持续发展，几年后患者可能会难以自主呼吸。全球 ALS 患者数量呈上升趋势，预计到 2040 年将有超过 30 万人患有该病。

FUS-ALS is caused by mutations in the FUS gene. It is the second most common causative gene for ALS in Japan and the third or fourth most common in Europe and the United States. Unlike typical ALS, FUS-ALS is more common in younger people, with the average age of onset being around 40, and is characterized by extremely rapid progression of the disease.

FUS-ALS 是由FUS基因突变引起的。它是日本第二大最常见的 ALS 致病基因，也是欧洲和美国第三或第四大最常见的 ALS 致病基因。与典型的 ALS 不同，FUS-ALS 在年轻人中更为常见，平均发病年龄在 40 岁左右，并且疾病进展极快。

This drug candidate, discovered and developed by Ionis, aims to treat FUS-ALS, a neurodegenerative condition caused by the accumulation of abnormal FUS protein in neurons due to a genetic mutation, by inhibiting production of the mutated FUS protein. Delivery is by intrathecal administration every 12 weeks. Ionis is conducting the ongoing phase 3 trial for ulefnersen in multiple countries, including Japan, subject to cost reimbursement by Otsuka starting in 2025. If development and then regulatory reviews proceed successfully, ulefnersen could become the first treatment for FUS-ALS.

这种候选药物由 Ionis 发现和开发，旨在通过抑制突变 FUS 蛋白的产生来治疗 FUS-ALS，这是一种由基因突变导致的异常 FUS 蛋白在神经元中积累而引起的神经退行性疾病。每 12 周通过鞘内给药一次。Ionis 正在包括日本在内的多个国家开展 ulefnersen 的 3 期试验，费用将从 2025 年开始由大冢报销。如果开发和监管审查顺利进行，ulefnersen 可能成为 FUS-ALS 的首个治疗药物。

Under the terms of the agreement, Otsuka will pay Ionis an upfront payment of U.S. $10 million, plus milestone payments based on achievement of regulatory approvals and sales targets. Ionis is also eligible to earn royalties on product sales. Otsuka will apply for regulatory approvals and exclusively carry out manufacturing and sales of the product worldwide.

根据协议条款，大冢将向 Ionis 支付 1000 万美元的预付款，并根据监管部门批准和销售目标的实现情况支付里程碑付款。Ionis 还有资格获得产品销售的特许权使用费。大冢将申请监管部门批准，并在全球范围内独家生产和销售该产品。

Makoto Inoue, president and representative director of Otsuka Pharmaceutical Co., Ltd. commented, "Otsuka Pharmaceutical is committed to the global development of treatments for rare diseases such as autosomal dominant polycystic kidney disease (ADPKD), IgA nephropathy, lupus nephritis, hereditary angioedema (HAE) and phenylketonuria (PKU) in order to respond to insufficiently medical needs. Through our expanded collaboration with Ionis Pharmaceuticals, we will strive to contribute to the treatment of patients worldwide with ALS accompanied by FUS mutations."

大塚制药株式会社总裁兼代表董事井上诚表示：“大塚制药致力于在全球范围内开发治疗常染色体显性多囊肾病 (ADPKD)、IgA 肾病、狼疮性肾炎、遗传性血管性水肿 (HAE) 和苯丙酮尿症 (PKU) 等罕见疾病的药物，以满足医疗需求。通过扩大与 Ionis Pharmaceuticals 的合作，我们将努力为全球伴有 FUS 突变的 ALS 患者的治疗做出贡献。”