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Research and Development

New light on small molecule medicine

Research and Development

Pipeline

Indication
Research
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clinical
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Anti-DNA Virus Program
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Anti-RNA Virus Program
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Neurodegenerative Program
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Cervical intraepithelial neoplasia

1. Causes and characteristics of the disorder

Cervical cancer is caused by long-term infection of the basal cells of the cervix with human papillomavirus (HPV) types 16, 18, 31, 33, 35, 45, 52 and 58. Persistent HPV infection leads to cervical dysplasia (cervical intraepithelial neoplasia), which often takes more than 10 years to progress to cervical cancer. Cervical intraepithelial neoplasia (CIN) is classified as CIN1 to CIN3, depending on the extent of the disease, and while partial resection is recommended for more advanced stages of CIN, there is no treatment for mild to moderate conditions, leaving patients with no choice but to be followed up.

The WHO executive board designated accelerating the elimination of cervical cancer as a global healthcare problem in Jan. 2019. There are about 30 million and 10 million women suffer CIN1/2 and CIN3 respectively worldwide. Of those half million women develop cervical cancer and more than quarter million die each year. We are aware that the current situation is a serious issue for many women suffering CIN.

KinoPharma's compound is already in clinical trials in Japan and South Korea. Candidate medicine is administered in the pre-surgical phase of CIN and is intended to prevent the progression to cervical cancer by eliminating HPV from the cervix. We believe there is value in our efforts to establish a treatment for CIN, for which there is no alternative to surgery, as soon as possible.

2. Common prophylaxis and treatments

HPV vaccines (Gardasil and other products) have been approved for administration in young women and men before being sexually active as the prevention of HPV infection.
Follow-up observation is conducted for mild (CIN 1) and moderate (CIN 2) cervical intraepithelial neoplasia. Severe cases (CIN 3) undergo conization which surgically removes the area of abnormal uterine cervix while preserving the uterus, however this is associated with issues such as increased risk of premature birth.

Common wart

1. Causes and characteristics of the disorder

Warts are caused by the infection of human papillomavirus (HPV). HPV enters from small scars on the skin, causing infection to skin keratinocyte. The infected keratinocyte divides at a faster rate, which causes thickening of the epidermis in the infected area and forming warts. Typical warts that appear on the hand, foot, or face are called common warts, and are caused by human papillomavirus types 2, 27, and 57. Although warts appear in all age groups, children are especially susceptible and may suffer numerous warts.

2. Common treatments

Cryotherapy using liquid nitrogen is the usual treatment method. This method can cause pain. Since it is difficult to remove viruses in a short period, may require a prolonged treatment duration. No effective antiviral drugs are approved.

Condyloma acuminatum

1. Causes and characteristics of the disease

Condyloma acuminatum is a flat, dome-shaped, cauliflower-shaped, or pedunculated wart that develops around the genital and anal areas due to human papillomavirus (HPV types 6 and 11) infection. It is transmitted through sexual intercourse and in saunas and public bathrooms. It is generally not painful or itchy, but is prone to the formation and growth of new warts, and often recurs after treatment.

2. General treatments

Topical medications, cryotherapy, and laser therapy are used, but it is known to cause recurrence in many cases. Imiquimod, an immunostimulant, is often prescribed as a topical medication, but it is known to cause intense inflammation around the area of application. As with common warts, there is a need for safe and effective antiviral medications.

Epidemic keratoconjunctivitis

1. Causes and characteristics of the disorder

Epidemic keratoconjunctivitis (EKC) is an inflammation caused by infection of adenovirus types 8, 19, 37, 53, 54, and 56 in the conjunctiva, and is accompanied by keratitis. The condition is highly infectious.
The incubation period is 8 to 14 days, and involves sudden onset with edema of eyelids and lacrimation. It causes swelling of preauricular lymph nodes, and development of corneal inflammation decreases transparency, with opacity in case persisting for up to a few years. Adenovirus, the causative virus of EKC, is mainly spread by hand contact, and infection extends within workplaces, hospitals, and households where people engage in close physical contact.

2. Common treatments

No effective antiviral drugs are available. Symptomatic treatment such as steroid eye drops are typically prescribed.

Influenza

1. Causes and characteristics of the disease

Seasonal influenza is caused by infection with influenza A and B viruses and is a recurring epidemic around the world. Severe cases kill between 290,000 and 650,000 people a year worldwide. Influenza viruses are susceptible to mutation and change their antigenicity slightly from year to year, leading to repeated epidemics. They can also mutate significantly over a period of years to decades, and completely new subtypes can emerge, which are known as discontinuous antigenic mutations and have the potential to cause a pandemic.

2. General treatments

Several anti-influenza agents have been approved. The emergence of drug-resistant viruses has been reported for most of the approved drugs. This drug resistance and the potential for the emergence of large antigenic mutations necessitates the development of new antiviral drugs.

Dengue fever

1. Causes and characteristics of the disease

Dengue fever is an infectious disease caused by the dengue virus and transmitted by mosquitoes. Dengue fever starts with a sudden onset of fever, followed by a rash, headache, osteoarthritis, nausea and vomiting. The fever usually resolves 2-7 days after the onset of the disease, and the rash appears around the time the fever resolves. The disease can be particularly severe on reinfection, and in rare cases, it can develop into dengue hemorrhagic fever or dengue shock syndrome, which can be fatal if not treated promptly and appropriately.

Coronavirus infections (SARS and others)

1. Causes and characteristics of the diseases

A total of seven coronaviruses are known to infect humans, including four types of the cold syndrome and three types of severe pneumonia viruses of animal origin (SARS-CoV, MERS-CoV and SARS-CoV-2). The first four viruses cause common cold symptoms, but in most cases do not cause severe illness. The three severe pneumonia viruses can cause severe respiratory and other illnesses, such as COVID-19 caused by SARS-CoV-2, which is still raging around the world.

2. General treatments

The antiviral drug “remdesivir” has been approved against COVID-19, but the development and approval of more effective antiviral drugs are eagerly awaited.

Down syndrome

1. Causes and characteristics of the disease

Down syndrome is a group of congenital disorders that are caused by a total of three chromosomes (trisomy) on chromosome 21. It is characterized by delayed physical development, distinctive facial features, and mild intellectual disability. It appears in 1 per 1,000 births per year and is the most common genetic disorder in newborns. In patients with Down syndrome, Alzheimer's disease is known to occur at a high rate after the age of 40 years.

2. General treatments

Since Down syndrome is a chromosomal abnormality, there is currently no fundamental treatment for the condition. A Spanish research group has published the findings of a phase 2 clinical trial showing that a green tea extract, which has Dyrk1a inhibitory properties, improves cognitive function in patients with Down syndrome.

Alzheimer's disease

1. Causes and characteristics of the disorder

According to an estimate of Alzheimer's Disease International in 2015, one person in the world is diagnosed with dementia every 3 seconds. In Japan, a survey by a research group of the Ministry of Health, Labour, and Welfare showed that there are about 4.62 million patients with dementia as of 2012, which is expected to increase in the future. The brains of patients with Alzheimer's disease, which accounts for about half of the cases of dementia, shows accumulation of amyloid β and tau protein, which leads to neuronal death that causes symptoms such as forgetfulness. The cause of Alzheimer's disease has not been discovered and no curative treatment methods have been established; however, treatment for the abnormal aggregation of tau protein has gained attention in the recent years. The tau protein aggregated in the brain of the patient is hyperphosphorylated, suggesting a close relationship between the hyperphosphorylation of tau protein and neuronal death.

2. Common treatments

There are no curative treatment methods available at present.
Several drugs are used to improve the symptoms of dementia to a certain degree, and these take effect by increasing the neurotransmitters in the brain.