Multiple sclerosis (MS) is a chronic inflammatory demyelinating neurological disorder most commonly seen in young adults and is designated as an intractable disease by the Ministry of Health, Labour and Welfare of Japan. The average age at diagnosis is relatively young at around 32 years. Globally, more than 60,000 new cases are diagnosed each year, and approximately 2.9 million people are currently living with the disease.

In this disorder, inflammation caused by abnormal immune responses damages the myelin sheath that surrounds neuronal axons, resulting in demyelination. As a result, the transmission of neural signals becomes delayed or interrupted. This causes a wide range of neurological symptoms, including sensory disturbances, visual impairment, and motor paralysis. As the disease progresses, patients may experience significant reductions in mobility, and many eventually require the use of a wheelchair in daily life.

Approximately 85% of patients initially present with the relapsing–remitting form of the disease, characterized by alternating periods of relapse and remission, and typically transition to secondary progressive multiple sclerosis over the course of 10 to 15 years. Inflammatory lesions detectable by MRI are observed from the early stages of the disease. These lesions arise when disruption of the blood–brain barrier allows peripheral immune cells, including T-cells and B-cells, to enter the central nervous system, leading to demyelination and irreversible tissue damage.

Once the disease progresses to the secondary progressive stage, the frequency of MRI-detectable lesions decreases, and infiltration of peripheral immune cells is no longer observed during periods without MRI activity. However, “smoldering inflammation” persists within the central nervous system, driving ongoing disease progression. At this stage, existing therapies targeting peripheral T and B-cells show limited effectiveness, and treatment options for non-relapsing secondary progressive multiple sclerosis remain significantly restricted.

Smoldering inflammation, considered a central pathological mechanism in secondary progressive multiple sclerosis (SPMS), is thought to be driven by microglia, the resident immune cells of the brain. Addressing this pathology therefore requires a therapeutic approach that directly suppresses microglial activity within the central nervous system, rather than targeting peripheral immune cells as in conventional treatments.

A representative example of this approach is tolebrutinib, a highly CNS-penetrant Bruton’s tyrosine kinase (BTK) inhibitor. This drug is being developed for non-relapsing secondary progressive multiple sclerosis and its potential as a new treatment option is being investigated.

In addition, LAT1 is known to play a role in microglial activation through the transport of essential amino acids. Based on this insight, CNS-penetrant LAT1 inhibitors may represent a novel therapeutic strategy for secondary progressive multiple sclerosis by targeting microglia and suppressing their activation.

JPH034, which we are developing for non-relapsing secondary progressive multiple sclerosis, has been selected for the Fast Forward Research Grant from the U.S. National Multiple Sclerosis Society (NMSS), a highly competitive program known for its rigorous evaluation standards, and has been awarded USD 600,000 in funding. In addition, our company was selected for the AMED Drug Discovery Venture Ecosystem Program, which provided access to grant funding of up to approximately JPY 2 billion through the IPO stage.

From an intellectual property perspective, we have secured a global exclusive license from Georgetown University for method-of-use patents covering LAT1 inhibitors in central inflammatory diseases, including multiple sclerosis. This strengthens our exclusive position in both development and commercialization.

On the research and development front, mouse model studies conducted by Georgetown University demonstrated improvements in clinical scores, immunomodulatory and neuroprotective effects, and reductions in visual evoked potential (VEP) latency following treatment with LAT1 inhibitors. We are also conducting collaborative clinical research with the Turku PET Centre, where we confirmed that microglial activation, one of the key inflammatory drivers in the central nervous system—coexists with LAT1 expression at the demyelinated lesion level.