umedaptanib pegol (RBM-007) / RIBOMIC - LARVOL DELTA

Discovery of Aptamers and the Acceleration of the Development of Targeting Research in Ophthalmology. (PubMed, Int J Nanomedicine) - "Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders."

Journal • Review • Age-related Macular Degeneration • Diabetic Retinopathy • Eye Cancer • Fibrosis • Glaucoma • Immunology • Macular Degeneration • Ocular Melanoma • Oncology • Ophthalmology • Retinal Disorders • CTGF • NCL • TFRC • TGFB1

RAMEN: A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2 | N=40 | Completed | Sponsor: Ribomic USA Inc | N=22 ➔ 40

Enrollment change • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

TEMPURA: RBM-007 in Treatment naïve Exudative Age-related Macular Degeneration (clinicaltrials.gov) - P1/2 | N=5 | Completed | Sponsor: Maturi, Raj K., M.D., P.C. | Recruiting ➔ Completed | Trial completion date: Jul 2022 ➔ Mar 2022 | Trial primary completion date: Jun 2022 ➔ Feb 2022

Trial completion • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

TOFU: A Phase II Study of RBM-007 Alone and RBM-007 With Eylea® in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2 | N=86 | Completed | Sponsor: Ribomic USA Inc | Active, not recruiting ➔ Completed

Combination therapy • Monotherapy • Trial completion • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

RAMEN: A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2 | N=22 | Completed | Sponsor: Ribomic USA Inc | Active, not recruiting ➔ Completed

Trial completion • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

RAMEN: A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2; N=22; Active, not recruiting; Sponsor: Ribomic USA Inc; Recruiting ➔ Active, not recruiting; N=40 ➔ 22

Clinical • Enrollment change • Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Intravitreal RBM-007, a Novel Anti-angiogenic and Anti-scarring Agent, in Recalcitrant Exudative Age-Related Macular Degeneration Patients: Interim Safety Update on the Phase 2 TOFU and the RAMEN Extension Study (RS-LONDON 2021) - No abstract available.

TOFU: A Phase II Study of RBM-007 Alone and RBM-007 With Eylea® in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2; N=81; Active, not recruiting; Sponsor: Ribomic USA Inc; Recruiting ➔ Active, not recruiting

Enrollment closed • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Multiple Therapeutic Applications of RBM-007, an Anti-FGF2 Aptamer. (PubMed, Cells) - "An isolated inhibitory RNA aptamer against FGF2, named RBM-007, has followed an extensive preclinical study, with two clinical trials in phase 2 and phase 1, respectively, underway to assess the therapeutic impact in age-related macular degeneration (wet AMD) and achondroplasia (ACH), respectively. Moreover, showing broad therapeutic potential, preclinical evidence supports the use of RBM-007 in the treatment of lung cancer and cancer pain."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Genetic Disorders • Hypertension • Lung Cancer • Macular Degeneration • Oncology • Ophthalmology • Pain • Retinal Disorders • Solid Tumor • Wet Age-related Macular Degeneration • FGF2

TOFU: A Phase II Study of RBM-007 Alone and RBM-007 With Eylea® in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2; N=81; Recruiting; Sponsor: Ribomic USA Inc; Trial completion date: Jun 2021 ➔ Dec 2021; Trial primary completion date: Jun 2021 ➔ Dec 2021

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

TEMPURA: RBM-007 in Treatment naïve Exudative Age-related Macular Degeneration (clinicaltrials.gov) - P1/2; N=5; Recruiting; Sponsor: Maturi, Raj K., M.D., P.C.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

TEMPURA: RBM-007 in Treatment naïve Exudative Age-related Macular Degeneration (clinicaltrials.gov) - P1/2; N=5; Not yet recruiting; Sponsor: Maturi, Raj K., M.D., P.C.

Clinical • New P1/2 trial • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice. (PubMed, Sci Transl Med) - "When delivered by subcutaneous injection, RBM-007 restored defective skeletal growth in a mouse model of achondroplasia. We thus demonstrate a ligand-trap concept of targeting the cartilage FGFR3 and delineate a potential therapeutic approach for achondroplasia and other FGFR3-related skeletal dysplasias."

Journal • Preclinical • Endocrine Disorders • Genetic Disorders • Orthopedics • FGF2 • FGFR3

RAMEN: A Multi-Center, Open Label, Extension Study Assessing the Efficacy and Safety of Additional Intravitreal Injections of RBM-007 in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: Ribomic USA Inc

Clinical • New P2 trial • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

2020’s Potential Retina Milestones - "A pivotal trial in nAMD and a Phase 2 trial of the suprachoroidal drug-delivery platform are on deck for RGX-314 gene therapy for nAMD. Investigator Jeffrey S. Heier, MD, reported Phase 1/2A results that showed treated patients averaged 2.6 intravitreal injections over 12 months. In later cohorts, five of 12 and eight of 11 patients were free of intravitreal injections at six months."

Review

Ribomic announces first injection in the phase 2 clinical trial of RBM-007 (TOFU study) in subjects with wet age-related macular degeneration (Businesswire) - "RIBOMIC...today announced that first patient has received injection in the phase 2 trial of RBM-007 for the treatment of exudative age-related macular degeneration (AMD) in the United States. The first site started enrollment at the end of December 2019 and five sites are now active across the United States."

Trial status

Results of the Phase I/II SUSHI Study of Intravitreal RBM-007 in Exudative Age-Related Macular Degeneration (Macula 2020) - No abstract available

P1/2 data

TOFU: A Phase II Study of RBM-007 Alone and RBM-007 With Eylea® in Subjects With Wet Age-related Macular Degeneration (clinicaltrials.gov) - P2; N=81; Recruiting; Sponsor: Ribomic USA Inc

Clinical • Combination therapy • Monotherapy • New P2 trial

Ribomic --- significantly continued, phase 2 clinical trial of aptamer drug candidate RBM-007 started in the US [Google Translation] - "The company announced that a phase 2 clinical trial of the newly developed aptamer drug candidate RBM-007 (anti-FGF2 aptamer) for wet age-related macular degeneration has been started in the United States."

Trial status

Anti-angiogenic and anti-scarring dual action of an anti-fibroblast growth factor-2 aptamer in animal models of retinal disease (EURETINA 2019) - "B) Laser-induced choroidal neovascularization (CNV) was performed in both a mouse model and a rat model (male BN rats, 6 weeks old), applying slit-lamp laser irradiation to the retina-choroid (532 nm, 50 µm spot size, 120-240 mW for 0.1 sec), immediately followed by intravitreal injections via micro-syringes with 33-gauge needles with test substances: 1) saline vehicle, 2) ranibizumab (10 or 20 μg/eye), 3) RBM-007 (6 to 45 μg/eye), or 4) combination ranibizumab + RBM-007. Blockade of FGF2 with a novel aptamer, RBM-007, led to suppression of angiogenesis in 3 different animal models. The dual action of RBM-007 against both choroidal neovascularization and subretinal fibrosis in the rat model suggests novel mechanisms for potential treatment of neovascular AMD. Based on these preclinical data, in October 2018 we entered a phase 1/2a clinical study of RBM-007 in patients with refractory neovascular AMD."

Preclinical

Anti-angiogenic and anti-scarring dual action of an anti-fibroblast growth factor-2 aptamer in animal models of retinal disease (EURETINA 2019) - "B) Laser-induced choroidal neovascularization (CNV) was performed in both a mouse model and a rat model (male BN rats, 6 weeks old), applying slit-lamp laser irradiation to the retina-choroid (532 nm, 50 µm spot size, 120-240 mW for 0.1 sec), immediately followed by intravitreal injections via micro-syringes with 33-gauge needles with test substances: 1) saline vehicle, 2) ranibizumab (10 or 20 μg/eye), 3) RBM-007 (6 to 45 μg/eye), or 4) combination ranibizumab + RBM-007. Blockade of FGF2 with a novel aptamer, RBM-007, led to suppression of angiogenesis in 3 different animal models. The dual action of RBM-007 against both choroidal neovascularization and subretinal fibrosis in the rat model suggests novel mechanisms for potential treatment of neovascular AMD. Based on these preclinical data, in October 2018 we entered a phase 1/2a clinical study of RBM-007 in patients with refractory neovascular AMD."

Preclinical

Announcement of online publication of RBM-007 mediated therapy for AMD and presentation at EURETINA International Congress (Ribomic Press Release) - "RIBOMIC Inc....announced the progress report on RBM-007 that is published online today and will be presented in an upcoming international congress...These results together with the positive top-line clinical data of the SUSHI study will be presented in the EURETINA 2019 International Congress to be held during September 5-8 in Paris...."

P1/2 data

Anti-Angiogenic and Anti-Scarring Dual Action of an Anti-Fibroblast Growth Factor 2 Aptamer in Animal Models of Retinal Disease. (PubMed, Mol Ther Nucleic Acids) - "Pharmacokinetic studies of RBM-007 in the rabbit vitreous revealed high and relatively long-lasting profiles that are superior to other approved anti-VEGF drugs. The anti-angiogenic and anti-scarring dual action of RBM-007 holds promise as an additive or alternative therapy to anti-VEGF treatments for nAMD."

Journal • Preclinical

SUSHI: RBM-007 in Subjects witH ExudatIve Age-related Macular Degeneration (clinicaltrials.gov) - P1/2; N=9; Completed; Sponsor: Ribomic USA Inc; Recruiting ➔ Completed

Clinical • Trial completion

RIBOMIC announces positive top-line results from the phase 1/2a clinical trial of RBM-007 (SUSHI study) in subjects with wet age-related macular degeneration (Businesswire) - P1/2, N=9; SUSHI (NCT03633084); Sponsor: RIBOMIC, Inc; "RIBOMIC, Inc...announced positive top-line results from its SUSHI study, Phase 1/2a single ascending dose clinical study of RBM-007...in nine subjects with wet Age-Related Macular Degeneration (wet AMD). SUSHI study achieved the primary endpoint of safety and tolerability, and also demonstrated efficacy trends in favor of RBM-007....Planning for the next multi-dose Phase 2 clinical trial is underway and enrollment is expected to begin in 3Q of FY2019."

Enrollment status • New P2 trial • P1/2 data