Pipeline

RBM-007 for Achondroplasia

Description/Summary

Achondroplasia (ACH) is a rare disease that causes short stature (adult height of approximately 130 cm for males and approximately 125 cm for females) with short limbs. There is no effective treatment available, and this disease is designated as an intractable disease by the Ministry of Health, Labour and Welfare. This disease results mainly from a genetic defect in FGFR3 (fibroblast growth factor type 3 receptor). This genetic change causes the receptor to be overly active to growth factors such as FGF2, which leads to reduced growth of chondrocytes, resulting a short stature. ACH occurs in a frequency of 1 in approximately 25,000 normal live births and is estimated to affect approximately 250,000 people worldwide.
RBM-007 demonstrates therapeutic effects by inhibiting the binding of FGF2 to FGFR3 in a study using an animal model of ACH and patient-derived iPS (induced pluripotent stem) cells.

Public Supports

Publications

Dual therapeutic action of a neutralizing anti-FGF2 aptamer in bone diseases and bone cancer pain
Jin, L., Nonaka, Y., Miyakawa, S., Fujiwara, M., Nakamura, Y.
Mol Ther 24(11): 1974-1986 (2016). doi: 10.1038/mt.2016.158

RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia
Kimura, T., Bosakova, M., Nonaka, Y., Hruba, E., Yasuda K., Furakawa, S., et al.
Science Translational Medicine??05 May 2021: Vol. 13, Issue 592, eaba4226
doi: 10.1126/scitranslmed.aba4226

Multiple therapeutic applications of RBM-007, an anti-FGF2 aptamer.
Nakamura, Y.
Cells 2021, 10, 1617. doi: 10.3390/cells10071617

RBM-006 for Retinal disease,Proliferative Vitreoretinopathy,Glaucoma,Diabetic Retinopathy

Description/Summary

Proliferative vitreoretinopathy (PVR) is a disease in which fibrosis of retinal pigment epithelial (RPE) cells leads to the formation of a proliferative membrane in the vitreous cavity, often resulting in severe visual impairment such as retinal detachment and blindness. Currently no effective preventive measures in PVR exist.
Autotaxin is an enzyme that synthesizes the lipid mediator lysophosphatidic acid (LPA). Increased levels of LPA and autotaxin have been observed in several diseases caused by tissue fibrosis.
RBM-006 is an aptamer that inhibits autotaxin and has been shown to have excellent PVR prophylaxis effect in animal model studies.
collaboration with Professor Osamu Nureki, Department of Biological Sciences, Graduate School of Science, The University of Tokyo and others.

Publications

Structural basis for specific inhibition of autotaxin by a DNA aptamer
Kato, K., Ikeda, H., Miyakawa, S., Futakawa, S., Nonaka, Y., Fujiwara, M., Okudaira S, Kano K, Aoki, J., Morita, J., Ishitani, R., Nishimasu, H., Nakamura, Y., Nureki, O.
Nature Struct Mol Biol 23: 395-401 (2016). doi: 10.1038/nsmb.3200

Effect of Anti-Autotaxin　Aptamer on the Development of Proliferative Vitreoretinopathy
Hanazaki, H., Yokota, H., Yamagami, S., Nakamura, Y., Nagaoka, T.
Int. J. Mol. Sci. 24, 15926 (2023).

RBM-011 for Pulmonary Arterial Hypertension

Description/Summary

Pulmonary arterial hypertension (PAH) is a designated incurable disease that leads to right heart failure due to increased pulmonary arterial pressure by stenosis or occlusion of the pulmonary arteries. The estimated number of patients is approximately 75,000 in Japan, the United States and major European countries. The currently available drugs have only a major effect on the relaxation of the pulmonary artery smooth muscle, and no therapeutic drug has been developed whose main function is to suppress the hyperplasia of the pulmonary artery.
IL-21 is known to promote the proliferation of pulmonary artery smooth muscle cells and promote PAH pathology. RBM-011 is a promising candidate to provide a new treatment of PAH by inhibiting the action of IL-21.

Public Supports

RBM-010 for Osteoarthritis

Description/Summary

RBM-010 is a promising candidate to provide a new treatment of osteoarthritis by inhibiting the action of ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5), which is one cause of the progression of osteoarthritis.
Osteoarthritis is a disease that, for a variety of reasons, causes pain and swelling in joints in the knees, legs, arms, shoulder and other parts of the body and eventually results in the deformation of joints. The only treatments are drugs to reduce pain and swelling and joint replacement surgery. There are no drugs that can cure this disease.
There are more than 25 million people in Japan and more than 240 million people worldwide, who suffer from osteoarthritis. The number of people with this disease is expected to continue to grow as the world’s population ages. (Source: The Journal of Bone and Mineral Metabolism 2009, 27(5), 620-8/Osteoarthritis Cartilage, 2018 March; 26(3): 319-325)

RBM-009 for Severe asthma

Description/Summary

Severe asthma is defined as asthma that requires treatment with high-capacity inhaled steroids plus other long-term control medications. Patients with severe asthma have a reduced quality of life due to frequent shortness of breath and dyspnea, which significantly interfere with daily activities and sleep.
There are a certain number of patients with severe asthma who are poorly controlled or refractory to the standard therapies described above, and some of them suffer asthma attacks and even asthma death despite treatment.
In addition to inhaled steroids and bronchodilators, several antibody drugs have recently been approved and used in the treatment of severe asthma, but some patients with severe asthma cannot be controlled even with these antibody drugs, creating unmet medical needs.