Multiple sclerosis is a chronic inflammatory demyelinating neurological disease most commonly found in young adults and is included in the Ministry of Health, Labour and Welfare's designated intractable disease. The average age at diagnosis is relatively young at 32 years, with more than 60,000 new diagnoses worldwide each year, and there are currently approximately 2.9 million patients.

In this disease, inflammation caused by the immune response damages (demyelination) the myelin that covers the axons of nerve cells, resulting in delayed or interrupted transmission of nerve signals. Therefore, various neurological symptoms such as sensory disturbances, visual impairments, and motor paralysis appear, and patients often have limb disabilities and are forced to live in a wheelchair.

Approximately 85% of patients develop relapsing-remitting form, which progresses through relapse and remission phases, and transitions to a secondary progressive type over 10~15 years. MRI findings (inflammatory lesions measured by MRI) are seen from the early stages of the disease, and when MRI findings occur, peripheral immune cells (T cells and B cells) invade the brain due to disruption of the blood- brain barrier, causing demyelination and irreversible tissue damage.

When the secondary progressive form progresses, the frequency of MRI findings decreases, and although peripheral immune cell infiltration is not seen during the absence of MRI findings, "smoldering inflammation" persists in the brain and the disease progresses. At this stage, existing drugs targeting obliterated T and B cells are ineffective, and treatment options for second-line progressive forms without relapse are still limited.

Smoldering inflammation, which is considered to be the central pathology of the secondary progressive type, is thought to be caused by microglia, which are immune cells that reside in the brain. Therefore, to address this pathology, a therapeutic approach is required in which drugs migrate into the brain and directly suppress microglial activity, rather than targeting peripheral immune cells as in the past.

In recent years, a representative example of this approach has been developed based on tolebrutinib, a BTK inhibitor with high central migration. The drug has shown efficacy in secondary progressive multiple sclerosis without relapse, and the first FDA approval for the same indication is expected to be obtained by the end of 2025.

On the other hand, it is known that LAT! is involved in the activation of microglia through essential amino acid transport. Based on this finding, it is suggested that targeting microglia with centrally transgomergable LAT! inhibitors and suppressing their activity may be a new treatment for secondary progressive multiple sclerosis.

JPH034 (for secondary progressive multiple sclerosis without relapse), which we are developing, has been selected for a Fast Forward Research Grant from the National Multiple Sclerosis Society (NMSS) in the United States, which is known for its extremely competitive and high evaluation standards, and has been awarded a grant of US$600,000. In addition, we have been selected by the Japan Agency for Medical Research and Development (AMED) in the drug discovery venture ecosystem, and have secured a grant of up to 2 billion yen that can be used until the IPO.

In terms of intellectual property, we have globally obtained the exclusive general license rights for the application patent of LAT! inhibitors for central inflammatory diseases (including multiple sclerosis) held by Georgetown University in the United States, strengthening our exclusive position in development and commercialization.

In terms of R&D, we are conducting joint clinical studies with Nordic universities to verify whether the activation of microglia, one of the inflammatory factors of the central nervous system, and the expression of LAT! coexist at the level of demyelinating lesions in a form that does not involve drug administration. In addition, we are preparing to start a Phase 1 clinical trial in the United States using AMED grants, and we have now prepared a data package for IND applications and completed the production of an investigational drug for the Phase 1 study. This allows us to steadily advance our plan to start a Phase 1 clinical trial in the United States within FY2025.