Ganciclovir is an antiviral drug that was commercialized in the 1980s and shows strong antiviral activity against DNA viruses such as herpes simplex virus and herpes zoster virus. There are several other antiviral drugs available for herpes, such as acyclovir, but these drugs are not effective against cytomegalovirus. In contrast, ganciclovir has strong antiviral activity against cytomegalovirus, and intravenous ganciclovir is used as a specific treatment for cytomegalovirus infection. It is not approved for the treatment of herpes simplex or varicella zoster virus in Japan.
　On the other hand, ganciclovir eye drops are approved and used for the treatment of herpes keratitis in Europe and the United States. It is not approved in Japan. In light of the antiviral properties of ganciclovir, the eye drops may be used for the treatment of the following ophthalmologic viral diseases.

　Cytomegalovirus is latently infectious and subclinical in most adults, but can multiply and cause inflammation in various organs when the immune system is weakened. In the case of the eye, cytomegalovirus proliferates in the corneal endothelium, causing corneal endotheliitis. Cytomegalovirus-induced corneal endotheliitis progresses slowly but does not heal spontaneously. If left untreated, it can lead to corneal edema, corneal opacity, and eventual blindness.
　Currently, treatment is either systemic intravitreal injection or in-hospital prescription ophthalmic solutions of ganciclovir, or both. We have already completed a clinical trial of eye drops for the treatment of corneal endotheliitis caused by cytomegalovirus, with positive results. We are currently preparing to submit an NDA, which is expected to be filed by the end of 2025, and the product will be launched in 2026. The drug has been designated as an orphan drug by the Ministry of Health, Labour and Welfare of Japan.

　In ocular tissues, herpes viruses mainly infect the corneal epithelium and often cause keratitis, but they can also infect the iris and ciliary body, causing anterior uveitis.
　Acyclovir ointment is the most commonly used treatment in Japan. Although acyclovir ointment is highly effective, it is not easy to apply to the eye and it is associated with a high incidence of corneal erosion.
　Unlike ointments, ganciclovir ophthalmic gel is easy to administer and does not cause corneal erosions. In addition, ganciclovir has a stronger antiviral effect against herpes than acyclovir, so its efficacy is comparable to that of acyclovir. Clinical trials have already been completed and an application is being prepared for the indication of herpetic keratitis.
　This product is developed in collaboration with Rohto Pharmaceutical Co. and Laboratoires Thea.

　ME104 has a chemical structure modified from oligosaccharides and is a compound similar to heparan sulfate, although it is a low molecular weight. Like heparin, a type of heparan sulfate, it prevents blood coagulation and is approved and used in injectable form as an anti-coagulant.
　Heparan sulfate, which has many sulfate groups such as heparin, binds to various proteins in vivo and affects their physiological activities. For example, it is well known that heparan sulfate increases the activity of certain growth factors and promotes tissue repair. We have also found that ME104, which is similar to heparan sulfate, promotes corneal epithelial cell growth and proliferation. Based on this discovery, we filed a patent application for a novel therapeutic agent for corneal disorders, which was registered in June 2024. (Patent No. 7514033)

　The corneal epithelium is a proliferative and reparative tissue that often heals quickly after damage. However, there are many cases of prolonged damage and intractable corneal disorders. In particular, it is known that damage to the sensory nerves distributed in the cornea causes prolonged corneal damage, and corneal disorders involving nerve damage are called neurotrophic keratopathy. The cornea has well-developed sensory nerves, and the nerves in the cornea not only transmit stimulus information to the brain but also secrete trophic factors, which are thought to be involved in the defense against corneal damage.
　Currently, there are no drugs available in Japan for the treatment of prolonged corneal disorders such as neurotrophic keratitis. Various growth factors that promote corneal epithelial cell proliferation are thought to be effective in treating corneal epithelial damage, but substances that strongly promote cell proliferation may also promote corneal angiogenesis. Although ME104's growth-promoting effect on corneal epithelial cells is weaker than that of epidermal growth factor, it is unlikely to induce angiogenesis and has an optimal profile as a treatment for corneal epithelial damage. It can be said to have an optimal profile as a treatment for corneal epithelial disorders.

　Dry eye is literally a type of corneal disorder in which the cornea is not adequately protected due to decreased tear fluid and other factors. Although the corneal epithelial cells are not significantly damaged, it causes eye discomfort and difficulty seeing. In recent years, due in part to the increased use of computers and smartphones, the number of patients is said to be about 2 million in Japan, and the number is increasing. Heparan sulfate is said to promote tissue building and repair, and ME104 eye drops are thought to maintain and repair corneal tissue for mild corneal disorders such as dry eye.

　Cutamesine is a sigma-1 receptor agonist. Sigma-1 receptors are located mainly in the endoplasmic reticulum, not on the cell membrane. Although there are still many unknowns about its function, it is basically thought to be involved in endoplasmic reticulum-mitochondrial activation, such as increasing ATP production, and to work in the direction of reducing cell damage. Sigma-1 receptor agonists act in a protective manner against various stresses, especially in neural tissues, which have little proliferative capacity. Although various compounds have been reported to act on sigma-1 receptor, most of them have low selectivity, and there are few compounds other than cutamesine that selectively act only on sigma-1 receptor. Cutamesine has potential for the treatment of a variety of neurological disorders and is currently being developed by a North American biotechnology company for the treatment of Amyotrophic Lateral Sclerosis.

　Amyotrophic lateral sclerosis (ALS) is an intractable neurological disease that causes motor deficits due to progressive damage to motor nerves. Sigma-1 receptor agonists have been reported to contribute to the recovery from motor nerve damage.