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Research and Development

Research and Development

Development of antiviral drugs

RKP00156

Candidate drug with antiviral effect against a broad range of DNA viruses.

Kinopharma works towards the development of new drugs with a novel concept, targeting the host kinase (protein kinase) rather than the virus itself.
This project enables to treat viral disorders which have no drug nor vaccine, as well as those with resistance to existing antiviral drugs.

1. What is a virus?

A virus is a simple microstructure consisting of a "capside" and "nucleic acid" contained inside. A virus infects other organisms (hosts) and utilize the proliferation mechanism of the host to replicate itself.
Through the replication of viruses, host cells may lead to deaths or canceration, and the host may suffer a variety of disorders.
In taxonomy, the virus is classified as DNA viruses and RNA viruses.

2. Mechanism of action

Conventional antiviral drugs suppressed viral activity by inhibiting the protein contained in or produced by the virus itself.
On the other hand, the antiviral drug developed by Kinopharma regulates the host enzyme used by viruses for replication and proliferation to inhibit the replication activity, thereby suppressing proliferation of the virus.

3. Target virus

Viruses are divided into two broad categories, which are RNA viruses (influenza viruses as the typical example) and DNA viruses (such as hepatitis B viruses and human papillomaviruses). While DNA viruses are the cause of a variety of disorders, there are only few drugs considered effective. Thus, we targets DNA viruses.

Types of virus (Baltimore classification)

Target viruses and disorders

Hepadnaviridae
HBV:Hepatitis B infection
Adenoviridae
ADV:Pharyngitis, epidemic keratoconjunctivitis, severe bronchiolitis (infants and children), acute myocarditis
Herpesviridae

HSV:Opportunistic infection with resistance to existing treatdrugs, encephalitis, etc.
FeHV:Feline herpes virus infection (conjunctivitis)

Papillomaviridae
HPV:Common and genital warts, cervical intrepithelial neoplasia (precancerous state)
Polyomaviridae
JCV:Progressive multifocal leukoencephalopathy (PML)
Parvoviridae
CPV:Canine parvovirus enteritis

Development of drugs
for neurodegenerative disorders

KPO1143

Candidate drug for neurodegenerative disorders such as Alzheimer's disease, based on the suppression of hyperphosphorylation of tau protein

1. Research on Alzheimer's disease

The root cause of Alzheimer's disease is not yet determined and research and development is being conducted with various approaches.
Many "amyloidβ (Aβ) targeted drugs" have been developed based on the hypothesis that Alzheimer's disease is caused by aggregation and deposition of Aβ. Clinical studies have not shown improvement in cognitive function as expected, resulting in the discontinuation of development of many candidate drugs.
Under these circumstances, "neurofibrillary tangles" have been found to correlate with neuronal loss, and tau protein has been attracting attention as a target for treatment for Alzheimer's disease.

2. Mechanism of action

Aggregation of tau protein is thought to be caused by hyperphosphorylation of tau protein.
"Dyrk1a" is a type of kinas, and thought to be a one of priming factors to the tau hyperphosphorylation.
KPO1143 has an effect of inhibiting "Dyrk1a" and is therefore thought to have a preventive effect on the onset of Alzheimer's disease.

Pipeline

Project No.
Research
Nonclinical
Phase I
Phase II
Phase III
Research
Nonclinical
Phase I
Phase II
Phase III
Research
Nonclinical
Phase I
Phase II
Phase III
Research
Nonclinical
Phase I
Phase II
Phase III
Research
Nonclinical
Phase I
Phase II
Phase III
step3-start
Compound
RKP00156
Indication
Common wart
Partner/grant
Kyoto University
AMED

1. Cause and characteristics of the disorder

Warts are caused by the infection of human papillomavirus (HPV), which is a type of DNA virus. 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 available.

Project No.002
Compound
RKP00156
Indication
Epidemic keratoconjunctivitis
Partner/grant
NEDO

1. Cause 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 prescrived.

Project No.003
Compound
RKP00156
Indication
Cervical intraepithelial neoplasia
Partner/grant
Kyoto University
KYOTO Industrial Support Organization 21

1. Cause and characteristics of the disorder

Cervical cancer is caused by the prolonged infection of human papillomavirus (HPV) types 16, 18, 31, 33, 35, 45, 52, and 58 in the basal cells of the uterine cervix. Persistent HPV infection causes dysplasia of the uterine cervix (cervical intraepithelial neoplasia), and many of these cases progress to cervical cancer over the period of 10 years or longer. Cervical intraepithelial neoplasia (CIN), which is the stage before cervical cancer, is classified into CIN 1 to 3 depending on the level of progression. At CIN 3, the surgical removal of the cervix area is typical tratment.There are no treatments available for CIN 1 and CIN 2 at present. 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 quarter million die each yeaa. We are aware that the current situation is a serious issue for many women suffering CIN. Preparation is under way for joint clinical studies with Kyoto University to develop RKP00156 as the treatment drug for CIN. The "antiviral drug" used for the clinical study is administered to patients before the stage where surgery is required for CIN and aims to prevent development to cervical cancer through the elimination of HPV.

2. Common prophyraxis 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.

Project No.004
Compound
KPO1143
Indication
Alzheimer's disease
Partner/grant
National Institute of Radiological Sciences

1. Cause 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.