Liquid Mine Co., Ltd.: Replacing Painful "Bone Marrow Tests" with "Blood Tests." Whole-Genome Analysis Monitoring to Detect Leukemia Recurrence Early

The Heavy Burden of Painful "Bone Marrow Tests" Tormenting Leukemia Patients

Hello, everyone. My name is Rinwa Kishimoto, CEO of Liquid Mine Co., Ltd. Thank you for having me today.

Under our vision, "To eliminate the pain of testing for leukemia patients and realize a society that can detect recurrence early," we are working on the social implementation of testing technology that monitors leukemia recurrence early using blood.

Leukemia is widely known as cancer of the blood. It develops due to genetic mutations, disrupting the balance of blood cells, causing severe anemia and bleeding, and ultimately leading to death. In Japan alone, there are over 14,000 new cases annually, and approximately 9,000 people die from leukemia each year, a number that is rising annually.

The most notable characteristic of leukemia is its extremely high recurrence rate compared to other cancers. Even with advanced treatments today, the recurrence rate is reported to be about 70%, and once it recurs, 70% of those patients lose their lives. Therefore, how quickly we can catch signs of recurrence during follow-up observations is a critical factor determining patient survival.

However, current follow-up testing faces three major challenges.
First, treatment is often conducted without accurately identifying the specific genetic mutations causing the disease for each patient.
Second, recurrence monitoring tests can only be applied to about 30% of all patients, leaving the remaining 70% unable to receive monitoring even if they want it.
Third, even the 30% of patients who can receive monitoring must repeatedly undergo the highly painful "bone marrow test (bone marrow aspiration)."

A bone marrow test involves inserting a thick needle, about 4 mm in diameter (comparable to the hole of a 5-yen coin), into the hip bone to aspirate bone marrow fluid, which is the manufacturing factory of blood. When pulling out this bone marrow fluid, a terrible, piercing pain runs through the patient. Leukemia patients must repeatedly undergo this painful test, which both doctors and patients agree they would prefer to never do again, just to monitor for recurrence.

Expanding the Applicability to 96% of Patients via Patented Whole-Genome Analysis Screening Technology

Through years of research and development at the Institute of Medical Science, the University of Tokyo, we have established a technology that completely replaces bone marrow tests with "painless blood tests." Our solution consists of two primary technologies.

The first is screening using "Whole-Genome Analysis."
To accurately identify the causative genetic mutation for each leukemia patient, we first analyze the patient's entire genome. We hold patented technology to selectively filter out normal genetic mutations unrelated to the disease from the data. This allows us to highly accurately isolate the "patient-specific target gene" directly involved in leukemia recurrence.

The second is "Recurrence Monitoring Tests Using Blood."
We manufacture tailor-made individualized testing agents matched to the identified target genetic mutations. This completely replaces traditional bone marrow tests with regular "blood tests (blood draws)."

With this technology, monitoring that was previously applicable to only about 30% of patients under traditional bone marrow tests can be expanded to "96% of patients" at once. This extremely high applicability rate has been clinically validated by data from our peer-reviewed paper published in *BLOOD*, a world-leading journal in hematology. In clinical data verifying the utility of our test on 53 patients with acute myeloid leukemia (AML), it was scientifically proven that our test using blood can predict recurrence with the same high sensitivity and precision as traditional tests using bone marrow fluid.

Dialogue with 102 Medical Institutions and the Challenge Toward Pharmaceutical Approval and Insurance Coverage

Currently, our technology is already receiving huge expectations from clinical sites. We have conducted direct interviews with hematology specialists at 102 medical institutions and 145 doctors nationwide, from Hokkaido University in the north to the University of the Ryukyus in the south. In surveys of doctors and patients, we have received zero negative opinions regarding our service, with many stating, "Introduce it as soon as possible" and "This is a revolutionary service."

In particular, 97% of doctors at clinical sites answered that they "strongly request pharmaceutical approval and national health insurance coverage (reimbursement) for this blood monitoring test," and we are currently holding close discussions with the Ministry of Health, Labour and Welfare and PMDA (Pharmaceuticals and Medical Devices Agency) toward pharmaceutical approval.

Our excellent technology development and social implementation efforts have been selected for major R&D startup grants from the government, such as AMED (Japan Agency for Medical Research and Development) and NEDO (New Energy and Industrial Technology Development Organization), and have received outstanding awards in venture championships hosted by the Ministry of Economy, Trade and Industry and the Tokyo Metropolitan Government.

The main purpose of today's presentation is to secure funding to further strengthen our patent portfolio. Currently, inquiries from doctors and medical institutions in the US and Europe are surging, asking to introduce this test to save their patients. Looking ahead to global expansion, we aim to quickly raise 30 million yen (bridge round) for global patent acquisition expenses. 20 million yen has already been committed, and we are looking for investors to join us for the remaining 10 million yen.

Please support our challenge to eliminate pain from patients and change the future of leukemia through the power of science. Thank you very much.

Q&A and Feedback

Mr. Toyama (Commentator): Thank you very much, Mr. Kishimoto. That was a wonderful pitch. Actually, one of my friends suffered from leukemia, so I had heard closely how painful the bone marrow test is and how much it drains patients mentally. Replacing that with a blood test is a wonderful medical innovation that will dramatically improve patients' QOL (Quality of Life).

Mr. Kishimoto: Thank you very much. Those words are the greatest motivation for our development. We want to save as many patients as possible who suffer mental distress just from going to the hospital due to the fear of bone marrow tests.

Mr. Toyama: That is a noble mission. On a business note, there have been recent news reports that the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry are tightening regulations (administrative notices, etc.) on non-medical private companies providing test services that notify disease risks. Since your service is developed entirely as a "medical device and testing program" in collaboration with doctors and medical institutions, does this tightening of regulations actually serve as a tailwind to eliminate competitors?

Mr. Kishimoto: Yes, exactly. Unlike private DTC (direct-to-consumer) genetic tests, our test is a highly clinical medical system where blood is collected through medical institutions based on doctor diagnoses and monitoring instructions, analyzed and reported by specialists. With our background at the Institute of Medical Science, the University of Tokyo, and as we hold professional discussions with PMDA aiming for pharmaceutical approval and insurance coverage, we believe that stricter regulations will strengthen the entry barriers for companies like us with solid medical evidence, securing our absolute advantage in the market.

Mr. Toyama: I see. Walking the orthodox path of medicine makes the tightening of regulations serve as a protective barrier. You mentioned targeting the US and Europe for future global expansion. Could you tell us more about the status of your entry plans and the patent expenses that are the focus of today's Ask?

Mr. Kishimoto: Yes. The US and Europe have very high numbers of leukemia patients and established medical infrastructure for molecular targeted drugs and genetic analysis, creating a high demand for our whole-genome screening and individualized testing agents. We have already received contact from local doctors, and to proceed with local joint clinical studies early, we first need to secure our basic patents globally. As a pre-round to Series A, we are looking for investors who can join us for the remaining 10 million yen allocation, or partners who can introduce us to medical alliances in the US and Europe.

Mr. Toyama: This is a very attractive project. I would definitely like to introduce you to medical-focused VCs, investors, and overseas networks in my circle. Thank you for your time today.

Mr. Kishimoto: Thank you very much. We look forward to it.