Confirming the safety of the new nucleic acid drug MIRX002 for malignant pleural mesothelioma - Possibility of a new treatment, the world's first microRNA cancer drug -

• Two clinical trials (single-dose study and multiple-dose study) of the new nucleic acid drug MIRX002 targeting patients with malignant pleural mesothelioma for whom standard treatments are ineffective or for which there is no appropriate treatment have been completed, and the primary endpoints of safety and tolerability were confirmed in both studies.
• No problematic side effects were observed even after repeated administration up to three times, indicating that continuous administration is possible.
• The results of this research are the first in the world to demonstrate a tolerable clinical safety profile for a microRNA cancer treatment, and demonstrate the possibility of a new treatment for malignant pleural mesothelioma.

The research group includes Professor Hidetoshi Tahara (principal investigator) of the Laboratory of Cell and Molecular Biology, Graduate School of Medical Sciences, Hiroshima University, and Professor Morito Okada (coordinating clinical trial physician) of the Department of Respiratory Surgery, Atomic Bomb Radiation Medical Research Institute, is a research group led by PURMX Therapeutics Co., Ltd. (Headquarters: Hiroshima City, President and CEO) In collaboration with CEO: Hidetoshi Tahara), we have been conducting clinical trials for the new nucleic acid drug MIRX002, targeting the rare cancer "malignant pleural mesothelioma," which is strongly suggested to be related to asbestos exposure.
MIRX002 is a nucleic acid drug whose active ingredient is miR-3140-3p, a natural microRNA that exists in humans. A single-dose study (MIRX002-01 study) and a multiple-dose study (MIRX002-02 study) of ``microRNA replacement therapy,'' which replenishes miR-3140-3p, which is deficient in cancer cells, have recently been completed, and in both studies, the main objective of ``safe administration with minimal side effects'' was achieved.
The clinical trial period (from the first administration date to the last observation date) was from January 12, 2022 to June 23, 2025, and from December 13, 2022 to September 16, 2025, respectively, and was conducted at three domestic facilities: Hiroshima University Hospital, Kinki University Hospital, and Hyogo College of Medicine Hospital.
In the clinical development of cancer therapeutics using microRNA, there have been reports of serious immune-related adverse events occurring in clinical trials using systemic administration (intravenous administration), resulting in the discontinuation of development (Phase I trial of miR-34a mimic "MRX34" by Mirna Therapeutics, Inc. in the US). In contrast, MIRX002 has adopted a strategy to minimize systemic exposure by using intrathoracic administration (local administration) to deliver the drug directly to the vicinity of the lesion, and in this study, it was the first microRNA cancer treatment drug in the world to demonstrate an acceptable safety profile in the clinical setting.

Malignant pleural mesothelioma is a rare malignant tumor that develops in the mesothelial cells that line the inner surface of the thoracic cavity.Although it has been strongly suggested that it is related to asbestos exposure, the details of its mechanism of occurrence remain unknown. The number of infected patients in Japan is predicted to peak around 2030 and reach approximately 3,000 people per year. Although the treatment paradigm is changing significantly with the introduction of immune checkpoint inhibitors, cancer is often advanced by the time it is diagnosed and treatment options are limited, so there is a strong need to develop treatments that suppress cancer growth using new mechanisms.

"miR-3140-3p" is a microRNA whose expression increases with cellular aging and has been identified as a promising nucleic acid drug candidate that exhibits antitumor effects against both "cancer stem cells" and "drug-resistant cancer cells."It has been confirmed that the expression level of miR-3140-3p is decreased in malignant pleural mesothelioma tissues and cell lines. MIRX002 is a "microRNA replacement therapy" that supplements the deficient miR-3140-3p, and is a drug that aims to induce cell death in malignant pleural mesothelioma cells and suppress cancer progression. Furthermore, by directly administering the drug into the thoracic cavity of patients with malignant pleural mesothelioma, it may be possible to deliver the drug close to the cancer and reduce systemic side effects.

In Study MIRX002-01 (single-dose study), a single dose of MIRX002 was administered intrathoracically to nine patients, three in each of three dose groups, in patients with malignant pleural mesothelioma who were ineffective for standard treatments or for whom existing treatments were not appropriate. No clinically relevant side effects were observed, indicating that the drug can be safely administered up to the highest dose.
In the MIRX002-02 study (repeated administration study), MIRX002 was administered intrathoracically up to three times at 28-day intervals to a total of four patients who participated in the MIRX002-01 study and were judged to have no safety issues and could be expected to be therapeutically effective. No increase in side effects was observed with repeated administration, indicating that the drug can be safely administered up to three times.
The results of this research are valuable data that demonstrate that MIRX002, a nucleic acid drug whose active ingredient is microRNA miR-3140-3p, can be safely administered intrathoracically to patients with malignant pleural mesothelioma, and we believe that this study has the potential to become a treatment option in the future as a treatment with few side effects.
 

Based on the data obtained this time, PURMX Therapeutics, Inc. is preparing for the next stage of clinical trials (global P1/2 trials), including overseas. In 2024, we received scientific advice from the U.S. Food and Drug Administration (FDA) in a pre-IND consultation and have begun building an international clinical trial system.
In addition, in a joint research course with the Cell and Molecular Biology Laboratory of the Hiroshima University Graduate School of Medical Sciences, we are continuing basic research on the mechanisms of action of MIRX002 and other microRNAs, and are preparing the data necessary for future approval applications.
Going forward, we will accelerate the development of this product through testing on a larger number of patients so that it can be used as an actual treatment.

Antitumor effect of MIRX002:
When a malignant pleural mesothelioma cell line was transplanted into the thoracic cavity of a mouse and MIRX002 was administered intrathoracically three times a week, tumor growth was suppressed for 3 weeks, and the survival period was also extended.
 

・Phase I study:
This is a trial in which a new drug is administered to humans (patients) for the first time. The drug's safety, appropriate dosage, and method of administration are investigated by gradually increasing the dosage in a small number of patients. In the case of anti-cancer drugs, they are usually targeted at patients for whom standard treatments do not/are not effective.
・Malignant pleural mesothelioma:
It is a rare malignant tumor (cancer) that primarily occurs in the pleura, and it is said that many people who develop this disease have worked or lived in environments where asbestos is often inhaled. If resection is possible, surgery is performed, but if resection is difficult or if the tumor recurs after surgery, chemotherapy is performed.

microRNA:
●definition: MicroRNA is a small RNA molecule of about 22 bases in length that is produced in the human body, and about 2,600 types are known as functional microRNA. These are a type of non-coding RNA and do not directly synthesize proteins.
●function: MicroRNAs regulate gene expression by binding to specific messenger RNAs (mRNAs) and suppressing their translation. A single microRNA can regulate the expression of more than 100 different genes, thereby playing an important role in cell function and developmental processes.
●biological role: MicroRNAs are involved in cell differentiation and development, as well as the onset of various diseases. In particular, its abnormal expression is viewed as a problem in pathological conditions such as cancer and cardiovascular disease.

Nucleic acid medicine:
Nucleic acid medicine is a general term for drugs whose basic skeletons are nucleotides and their derivatives, which constitute nucleic acids (DNA and RNA) synthesized in vivo.

PURMX Therapeutics Co., Ltd.:
This is a bioventure from Hiroshima University that was established in January 2021 by Professor Hidetoshi Tahara of the Cell and Molecular Biology Laboratory, Graduate School of Medical Sciences, Hiroshima University.