Ashvattha Therapeutics has presented preclinical data on its anti-angiogenic precision nanomedicine, D-4517.2, at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting. The new class of nanomedicine therapeutics selectively targets activated cells in areas of inflammation. Ashvattha has demonstrated that D-4517.2 reduces choroidal neovascularization (CNV) lesions by targeting activated microglia and hypertrophic retinal pigment cells, which are innovative cells responsible for increased vascularisation associated with neovascular age-related macular degeneration (wet AMD) and diabetic macular oedema (DME).
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Two preclinical data sets were presented at the event, demonstrating the efficacy of the anti-VEGF nanomedicine in a laser-induced CNV mouse model and a VLDLR−/− mouse model. The first data set showed that a single oral dose of D-4517.2 significantly reduced CNV lesions to a level comparable to administration using subcutaneous and intravitreal methods. The second data set showed that oral and subcutaneous administration of D-4517.2 reduced CNV lesions by targeting activated microglia and macrophages in the choroid and retina.
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These preclinical studies support the development of D-4517.2 as an oral treatment for neovascular age-related macular degeneration (wet AMD) and diabetic macular oedema (DME), with the potential to eliminate burdensome intravitreal injections for patients. Furthermore, compared to current treatments that rely on direct eye injections, D-4517.2 may reduce the treatment burden on patients.
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Jeff Cleland, CEO, co-founder, and chairman of Ashvattha Therapeutics, remarked that “patients suffering from wet AMD and DME often have to endure injections directly into the eye at a specialist’s office in order to find any relief. This data supports the development of an oral formulation of D-4517.2 as an alternative to injections while greatly reducing the treatment burden on patients.”
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Natacha Le Moan, Head of Translational Sciences at Ashvattha, gave an oral presentation titled “Oral Formulation Development of the Anti-Angiogenesis Drug D-4517.2 to Treat Age-related Macular Degeneration (wet AMD) and Diabetic Macular Edema (DME)” at the meeting. She discussed the efficacy of the oral formulation of D-4517.2 in a mouse model of wet AMD. The key highlights of the presentation were that a single subcutaneous dose of D-4517.2 (40 mg) significantly reduced CNV lesion area by 2-fold compared to vehicle control and a single oral dose of D-4517.2 (40 mg) also significantly reduced CNV lesion area and vascular leakage by 2-fold. A 200 mg oral dose further reduced the CNV lesion area by 3.5 fold.
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Meanwhile, Elia Duh, a collaborator from Johns Hopkins University, presented a poster titled “Suppression of subretinal neovascularization in Vldlr knockout mice by systemic administration of a targeted VEGF-receptor inhibitor,” discussing the cellular localization and efficacy of D-4517.2 in a wet AMD mouse model. The study evaluated the localization of D-4517.2 in VLDLR−/− mice, an animal model with symptoms of Type III wet AMD after birth. The results showed that the nanomedicine conjugated with a fluorophore (D-Cy5) colocalized with activated microglia and macrophages within regions of ocular inflammation in Vldlr-/- mice.
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Overall, the preclinical data presented by Ashvattha supports the development of D-4517.2 as a preventive treatment for neovascular age-related macular degeneration (wet AMD) and diabetic macular oedema (DME). Ashvattha’s precision nanomedicines selectively target regions of inflammation at a cellular level and cross biological barriers, including the blood-retinal barrier. Once ready for clinical trials, D-4517.2 could pave the way for improved precision medicine and less-invasive treatments for these debilitating conditions.
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