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. Neovascular AMD is also known as wet 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.^*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. These drugs inhibit vascular endothelial growth factor (VEGF), which plays a key role in the formation of abnormal blood vessels.

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.

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

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.

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. 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."

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. 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."

Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema

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.

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.

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

1. https://www.nanbyou.or.jp/entry/2434
2. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-presents-positive-60-week-results-4d-150-spectra-clinical

About Otsuka

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. Otsuka's unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide.

For further information, please visit www.otsuka.co.jp/en/

About 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.

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.