Otsuka Pharmaceutical Co., Ltd. (Otsuka) announces that it has entered into a license agreement with 4D Molecular Therapeutics, Inc. (Nasdaq: FDMT; 4DMT), based in California, to obtain exclusive rights for the development and commercialization of 4D-150, a therapeutic candidate for the progressive eye disease nAMD (neovascular age-related macular degeneration) and DME (diabetic macular edema), in Asia and Oceania, including Japan.

大塚制药株式会社（Otsuka）宣布，已与总部位于加利福尼亚的4D Molecular Therapeutics, Inc.（纳斯达克代码：FDMT；4DMT）达成许可协议，获得在亚洲和大洋洲（包括日本）开发和商业化用于治疗进展性眼病nAMD（新生血管性年龄相关性黄斑变性）和DME（糖尿病性黄斑水肿）的候选药物4D-150的独家权利。

Neovascular AMD is also known as wet AMD..

新生血管性AMD也被称为湿性AMD。

AMD is one of the leading causes of vision impairment among the elderly. In Japan, approximately 1.3% of individuals aged 50 and older are affected, with nAMD accounting for the majority of cases at 1.2%. This corresponds to an estimated patient population in Japan of around 690,000.

年龄相关性黄斑变性（AMD）是老年人视力障碍的主要原因之一。在日本，约有1.3%的50岁及以上人群受到影响，其中新生血管性年龄相关性黄斑变性（nAMD）占大多数，约为1.2%。这相当于日本大约有69万名患者。

*1

*1

In nAMD, fragile new blood vessels develop in the macula, the central part of the retina. These vessels leak blood and other components, leading to hemorrhage and edema. If left untreated, this can result in significant retinal damage. In recent years, the standard treatment has involved the intravitreal injection of anti-VEGF agents every 4 to 16 weeks.

在新生血管性年龄相关性黄斑变性（nAMD）中，视网膜中央部分的黄斑区域会形成脆弱的新血管。这些血管渗漏血液及其他成分，导致出血和水肿。如果不进行治疗，可能会造成严重的视网膜损伤。近年来，标准治疗方法是每4至16周进行玻璃体内注射抗VEGF药物。

These drugs inhibit vascular endothelial growth factor (VEGF), which plays a key role in the formation of abnormal blood vessels..

这些药物抑制血管内皮生长因子 (VEGF)，该因子在异常血管的形成中起关键作用。

However, the standard treatment of intravitreal administration of anti-VEGF agents has proven difficult to maintain over the long term, often resulting in insufficient suppression of disease progression. As a result, there has been a growing demand for anti-VEGF agents with longer-lasting effects.

然而，玻璃体内注射抗VEGF药物的标准治疗被证明难以长期维持，常常导致对疾病进展的抑制不足。因此，对抗VEGF药物的需求日益增长，这些药物需要具有更持久的效果。

4DMT's 4D-150 is a gene therapy designed to deliver multiple therapeutic genes into retinal cells using a novel adeno-associated virus (AAV) vector, a harmless virus. It is intended to broadly inhibit four members of the VEGF family and provide long-lasting effects through a single intravitreal injection.

4DMT的4D-150是一种基因疗法，旨在通过一种新型的无害腺相关病毒（AAV）载体将多种治疗基因递送到视网膜细胞中。该疗法意在广泛抑制VEGF家族的四个成员，并通过单次玻璃体内注射产生持久效果。

Clinical trials to date have demonstrated efficacy lasting up to 130 weeks..

迄今为止，临床试验已证明疗效持续长达130周。

*2

*2

Under the terms of the agreement, Otsuka will obtain exclusive rights from 4DMT to develop and commercialize 4D-150 for retinal vascular diseases, including nAMD and DME, in Asia and Oceania, including Japan. Otsuka will lead all regulatory and commercialization activities in its licensed territories, while 4DMT will continue to lead all Phase 3 clinical activities globally, including within the APAC region.

根据协议条款，大冢将从4DMT获得在亚洲和大洋洲（包括日本）开发和商业化用于治疗视网膜血管疾病（包括nAMD和DME）的4D-150的独家权利。大冢将主导其授权区域内的所有监管和商业化活动，而4DMT将继续主导全球范围内的所有第三阶段临床活动，包括亚太地区。

Clinical sites in the APAC region for 4FRONT-2, the global Phase 3 study in nAMD, are expected to open by the end of the year, with sites in Japan expected to open in January 2026. Otsuka will partially bear the development costs..

预计APAC地区针对nAMD的全球III期研究4FRONT-2的临床站点将在今年年底前启动，而日本的站点预计于2026年1月启动。大冢制药将部分承担开发费用。

Otsuka will make an upfront payment of $85 million to 4DMT, in addition to reimbursement of certain R&D expenses and milestone payments contingent upon the achievement of specified development and commercial targets. In addition, Otsuka will pay 4DMT tiered royalties based on net sales.

大冢将向4DMT支付8500万美元的预付款，此外还将报销某些研发费用，并根据达成特定开发和商业目标的情况支付里程碑款项。此外，大冢将基于净销售额向4DMT支付阶梯式特许权使用费。

Makoto Inoue, president and representative director of Otsuka Pharmaceutical Co., Ltd. commented, 'Otsuka Pharmaceutical has created new value that contributes to the well-being of patients in Japan and around the world through both in-house and collaborative research. Neovascular age-related macular degeneration and diabetic macular edema--conditions we are now addressing--cause visual field defects and vision loss, severely impacting daily life.

大塚制药株式会社社长兼代表董事井上诚表示：“大塚制药通过内部和合作研究，创造了为日本乃至全球患者福祉作出贡献的新价值。我们目前正在应对的新生血管性年龄相关性黄斑变性和糖尿病性黄斑水肿等疾病会导致视野缺损和视力丧失，严重影响患者的日常生活。”

These remain areas of significant unmet medical need, as current standard therapies are difficult to sustain over the long term. By introducing 4D-150 to the markets in Japan, and elsewhere in Asia and Oceania, we aim to help prevent vision loss through a single, potentially lifelong administration.'.

这些领域仍然存在显著的未满足医疗需求，因为当前的标准疗法难以长期维持。通过将4D-150引入日本及其他亚洲和大洋洲市场，我们的目标是通过一次可能终生有效的治疗来帮助预防视力丧失。

David Kirn, M.D., co-founder and chief executive officer of 4DMT, stated, 'We are thrilled to partner with Otsuka, whose global leadership and expertise make them an ideal partner for advancing care in retinal vascular diseases. This collaboration not only strengthens our global strategy but also addresses the significant unmet needs in APAC, where nAMD (also known as wet AMD) and DME are highly prevalent.

4DMT 联合创始人兼首席执行官 David Kirn 医学博士表示：“我们非常高兴能与大冢合作，大冢的全球领导地位和专业能力使他们成为推动视网膜血管疾病治疗的理想合作伙伴。此次合作不仅加强了我们的全球战略，还满足了亚太地区在这一领域显著未被满足的需求，尤其是在 nAMD（也称为湿性 AMD）和 DME 高度流行的地区。”

By leveraging Otsuka's deep local knowledge, we aim to accelerate the development and accessibility of 4D-150, expanding its reach to patients who need innovative, long-lasting therapies for potential treatment burden reduction and vision preservation.'.

通过利用大冢的深厚本地知识，我们旨在加速4D-150的开发和可及性，扩大其覆盖范围，为需要创新、持久疗法的患者提供潜在治疗负担减轻和视力保护。

Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema

新生血管性年龄相关性黄斑变性与糖尿病性黄斑水肿

Neovascular age-related macular degeneration (nAMD) is a condition in which choroidal neovascularization invades beneath the retinal pigment epithelium or between the retina and the retinal pigment epithelium, leading to retinal damage. Unlike normal blood vessels, these abnormal vessels are prone to leakage or rupture, resulting in retinal edema and the accumulation of subretinal fluid..

新生血管性年龄相关性黄斑变性（nAMD）是一种脉络膜新生血管侵入视网膜色素上皮下方或视网膜与视网膜色素上皮之间，导致视网膜损伤的疾病。这些异常血管不同于正常血管，容易发生渗漏或破裂，从而引起视网膜水肿和视网膜下液的积聚。

Diabetic macular edema (DME) arises as a complication of diabetic retinopathy. It is characterized by multiple capillary microaneurysms near the macula and leakage of blood components, which cause retinal swelling. DME can occur regardless of the severity of diabetic retinopathy and may lead to vision loss..

糖尿病性黄斑水肿 (DME) 是糖尿病视网膜病变的一种并发症。其特征是黄斑附近出现多个毛细血管微动脉瘤和血液成分渗漏，从而导致视网膜肿胀。DME 可发生在糖尿病视网膜病变的任何严重程度，并可能导致视力丧失。

In Japan, diabetic retinopathy and neovascular age-related macular degeneration are the third and fourth leading causes of visual impairment, respectively.

在日本，糖尿病性视网膜病变和新生血管性年龄相关性黄斑变性分别是导致视力障碍的第三和第四大原因。

About Otsuka

关于大冢制药

Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual's potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement.

大冢制药株式会社是一家全方位的医疗保健公司，专注于挖掘每个人的潜能以提升其健康水平。我们的医药相关业务提供针对身体和心理健康的治疗与诊断方案。我们的营养保健品业务则支持日常健康维护与改善。

Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: .

大冢的独特产品和服务基于科学证据，在我们企业理念的指导下：。

Otsuka-people creating new products for better health worldwide

大冢——为全球更健康创造新产品的人们

.

。

For further information, please visit

如需更多信息，请访问

www.otsuka.co.jp/en/

www.otsuka.co.jp/en/

About 4DMT

关于4DMT

4DMT is a late-stage biotechnology company advancing durable and disease-targeted therapeutics with potential to transform treatment paradigms and provide unprecedented benefits to patients. 4DMT's proprietary invention platform, Therapeutic Vector Evolution, combines the power of directed evolution with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our wholly owned and partnered product candidates..

4DMT是一家处于后期阶段的生物技术公司，致力于推进持久且针对特定疾病的有效治疗方法，有潜力转变治疗模式，并为患者提供前所未有的益处。4DMT的专有发明平台——治疗载体进化（Therapeutic Vector Evolution），将定向进化的强大能力与近十亿种合成AAV衣壳衍生序列相结合，以发明用于我们全资拥有及合作产品候选物的定制化和进化载体。

Its lead program, 4D-150, is a potential backbone therapy that is expected to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) targeted to the retina with a single intravitreal injection.

其主导项目4D-150是一种潜在的核心疗法，预计通过单次玻璃体内注射，可持续多年向视网膜提供抗VEGF（阿柏西普和抗VEGF-C）的靶向递送。