4D Molecular announces publication of 4D-150 preclinical data

4D Molecular (FDMT) Therapeutics announced the publication of landmark preclinical data demonstrating the potential of the Company’s proprietary Therapeutic Vector Evolution platform, intravitreal R100 vector and the R100-based genetic medicine 4D-150. Pioneering efficacy and safety results in a difficult-to-treat nonhuman primate model of wet age-related macular degeneration demonstrated the potential of 4D-150 to substantially reduce the treatment burden and improve long-term vision outcomes for patients with wet AMD, diabetic macular edema and diabetic retinopathy. The data were published in Investigative Ophthalmology & Visual Science; December 2024 issue. IOVS is the journal of the Association for Research in Vision and Ophthalmology, a leading basic and translational research association in ophthalmology. The publication entitled, “Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies,” reports the results of preclinical discovery, engineering and characterization studies evaluating the safety, retinal cell transduction, transgene expression and clinical activity of proprietary evolved intravitreal vector R100 and 4D-150, an R100-based genetic medicine carrying 2 therapeutic transgenes: a codon-optimized sequence encoding aflibercept, a recombinant protein that inhibits VEGF-A, VEGF-B and PlGF, and a microRNA sequence that inhibits expression of VEGF-C. The data showed that R100 demonstrated significantly superior human retinal cell transduction compared to AAV2, and intravitreal administration of 4D-150 to nonhuman primates was well tolerated and led to robust panretinal expression of both transgenes, especially within the macula region; AAV2 was unable to transduce deep retinal cell layers in the same model. In a difficult-to-treat primate laser-induced choroidal neovascularization model of wet AMD, 4D-150 completely prevented grade IV angiogenic lesions at all tested doses.