Clinical Trials

　　

Wet Age-related Macular Degeneration(wet AMD）

Age-related macular degeneration (AMD) affects approximately 1% of individuals aged 50 years or older and is the leading cause of vision loss in Western countries. As at 2014, of the 135 million AMD sufferers worldwide, some 12.25 million patients resided in the United States (Reference 1).

Drugs that can inhibit abnormal retinal angiogenesis (anti-VEGF drugs, such as Lucentis® and Eylea®) are available for treatment of wet AMD and they constitute a market worth around 1.5 trillion yen. However, currently available drugs, which have been in practical use for 17 years, have been found through follow-up research to have clinical issues:

These factors are likely to involve retinal scarring (fibrosis) caused by lesions (Reference 4). Currently available drugs have no inhibitory effect on scarring.

Our anti-FGF2 (fibroblast growth factor 2) aptamer, RBM-007 (Reference 5), inhibits not only angiogenesis but also scar formation in the retina. This dual action is a novel mechanism that currently available drugs do not have and is expected to provide a new therapeutic approach to patients who do not respond well to currently available drugs.

Three P2 clinical trials have been conducted in the USA to assess safety and efficacy of RBM-007 for wet AMD.

1.TOFU Study (Active-controlled, double masked trial)
https://clinicaltrials.gov/ct2/show/study/NCT04200248

2. RAMEN Study (Single-arm, open-label extension trial)
https://clinicaltrials.gov/ct2/show/NCT04640272

3. TEMPURA study (Investigator sponsored trial in treatment naïve wAMD patients).
https://clinicaltrials.gov/ct2/show/NCT04895293?term=NCT04895293&draw=2&rank=1

Throughout these studies RBM-007 was safe, well tolerated, and effective to treat wet AMD patients with no or short history of anti-VEGF treatment (Reference 6, 7). Striking improvements in visual acuity and anatomy were observed in some of the treatment naive patients. In wet AMD patients with a long history of anti-VEGF treatment, RBM-007 showed no additional benefit of monotherapy or the combination over Eylea®. Nevertheless, the pre-existing fibrosis remained stable without worsening in these studies. Notably, visual acuity decreased slightly in patients who switched from anti-VEGF to RBM-007. Therefore, we believe that RBM-007 is an excellent alternative as a first-line medication before patients are exposed to anti-VEGF treatments to mitigate risk of damage caused by fibrosis. Further studies are needed on the efficacy of RBM-007 early in the onset of wet AMD as well as in coordination or combination with anti-VEGF drugs.

References

Achondroplasia

Background: Achondroplasia is a rare disease affecting approximately one in 25,000 newborns. With few effective treatments available, it represents an unmet medical need, necessitating the development of novel therapeutic agents. This rare disorder arises from mutations in FGFR3, a fibroblast growth factor receptor, and is primarily characterized by short stature due to limb shortening. To date, we have successfully demonstrated the non-clinical proof of concept (POC) for RBM-007 (international nonproprietary name : umedaptanib pegol) in pharmacology studies using achondroplasia model mice (mice with the FGFR3 gene artificially modified to the disease-causing mutation). These studies confirmed RBM-007's efficacy in improving short stature, specifically for achondroplasia. Furthermore, it is known that induced pluripotent stem cells (iPSCs) derived from achondroplasia patients exhibit impaired differentiation into chondrocytes. However, we have demonstrated that adding RBM-007 during in vitro culture of these iPSCs enables differentiation into chondrocytes. Moreover, when these differentiated cells were transplanted into immunodeficient mice, chondroid tissue formed within the mice (joint research with Osaka University School of Medicine). These results strongly suggest that RBM-007 has the potential to become a new drug for achondroplasia.

Clinical Trial Progress: From fiscal year 2021 for three years, we received funding as part of AMED's Rare Disease Drug Designation Pre-Commercialization Support Program. This funding aims to conduct a Phase 2 observational study to collect clinical baseline data, including height growth, in pediatric ACH patients (ages 5 to 14) and to select subjects for the Phase 2 clinical trial. These studies include a Phase 2 observational study, a Phase 2 clinical trial to evaluate the efficacy and safety of RBM-007 in pediatric ACH patients, and a subsequent Phase 2 long-term administration study. Patient enrollment for the Phase 2 observational study (26 weeks) began in November 2022. Thirteen pediatric ACH patients were enrolled across eight sites in Tokyo, Okayama, and the Kansai region. The observation period for the final case was completed in December 2024. For the Phase 2 clinical trial, dosing commenced in April 2023: Cohort 1 (low-dose group, 6 patients, 0.3 mg/kg subcutaneous injection once weekly for 26 weeks) and Cohort 2 (high-dose group, 6 patients, 0.6 mg/kg subcutaneous injection once every two weeks for 26 weeks). Dosing was completed in September 2025. Of the 12 subjects who completed the Phase 2 clinical trial, 11 have transitioned to a Phase 2 long-term administration study under the same dosing conditions, where the efficacy and safety of the investigational drug continue to be evaluated.

Summary of Trial Results: For Cohort 1, excluding one subject who discontinued treatment early, three of the five subjects showed an increase in height growth velocity compared to the pre-treatment period (observational study). Among these three, two subjects showed a significant increase of +4.6 cm/year and +3.3 cm/year, respectively. The two subjects in Cohort 1 who showed a marked increase in height growth rate have transitioned to the Phase 2 long-term administration study. The effect of increased height growth rate was sustained even after 2 years of continued administration. For Cohort 2, an increase in height growth velocity was confirmed in 5 of the 6 subjects compared to the pre-treatment (observation study) period. Among these, two subjects showed a marked increase of +5.0 cm/year and +2.0 cm/year, respectively. The mean height growth velocity in the Phase 2 clinical trial was +1.5 cm/year for Cohort 1 and +1.4 cm/year for Cohort 2, comparable to the mean height growth velocity of +1.7 cm/year※2 for Voxzogo® (hereinafter referred to as the “approved drug”). Furthermore, in two pediatric patients with a history of treatment with the approved drug, the height growth rate improved by +1.1 cm/year and +2.0 cm/year, respectively, after administration of RBM-007. Furthermore, no safety concerns have been observed in pediatric ACH patients treated with RBM-007 to date. Based on the results from Cohort 1, the Company submitted an Orphan Drug Designation (ODD) application to the Ministry of Health, Labour and Welfare (MHLW) in Japan, which was approved in May 2025. Consequently, the Company applied for and received approval for a grant from the National Institute of Biomedical Innovation, Health and Nutrition (NIBN). Currently, considering the results of the Phase 2 clinical trial and other factors, we are planning to conduct a Phase 3 clinical trial (once weekly subcutaneous administration of 1 mg/kg, target patient age: approximately 2 years and older) and are consulting with the Pharmaceuticals and Medical Devices Agency (PMDA).

[Information of the RBM-007 phase 1 study in Japan]

[Information of the RBM-007 early phase 2 observational study in Japan]

[Information of the RBM-007 early phase 2 study in Japan]

[Information of the RBM-007 early phase 2 extension study in Japan]

References

The list above, as well as information from RIBOMIC-sponsored clinical trials registered and published on registries such as ClinicalTrials.gov and JapicCTI/jRCT, are provided for informational purposes only, and are not intended to promote any product.