Ashvattha Therapeutics Presents Preclinical Data on anti-VEGF Nanomedicine D-4517.2 at the 2023 ARVO Annual Meeting

  • Data demonstrated that a single oral dose of D-4517.2 significantly reduced choroidal neovascularization (CNV) lesions to a level comparable to D-4517.2 delivered subcutaneously and Aflibercept administered intravitreally at the same mass dose in a laser-induced CNV mouse model 
  • Findings from a second preclinical study in a VLDLR−/− mouse model demonstrated oral and subcutaneous administration of D-4517.2 reduces CNV lesions by targeting activated microglia and macrophages in the choroid and retina 
  • These preclinical data support the development of D-4517.2 as an oral treatment for neovascular age-related macular degeneration (wet AMD) and diabetic macular edema (DME) with the potential to eliminate burdensome intravitreal injections for patients 


REDWOOD CITY, Calif., April 26, 2023 – Ashvattha Therapeutics (“Ashvattha”), a clinical-stage company advancing a new class of nanomedicine therapeutics that transverse tissue barriers to selectively target activated cells in regions of inflammation, today announced two preclinical data sets demonstrating the efficacy of its anti-angiogenic precision nanomedicine, D-4517.2. The data were shared in an oral presentation and poster at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting held on April 23-27, 2023 in New Orleans, LA.

D-4517.2 is a novel precision nanomedicine that inhibits neovascularization by targeting activated microglia and hypertrophic retinal pigment cells, cells responsible for the increased vascularization associated with neovascular age-related macular degeneration (wet AMD) and diabetic macular edema (DME).

“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,” said Jeff Cleland, CEO, co-founder, and chairman of Ashvattha Therapeutics. “The preclinical data also builds on previous findings that demonstrate our precision nanomedicines selectively target regions of inflammation at a cellular level and cross biological barriers including the blood-retinal barrier.”

Natacha Le Moan, Ph.D, 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)” in which she discussed the efficacy of the oral formulation of D-4517.2 in a mouse model of wet AMD.

Key highlights from presentation:

  • Results indicated that a single subcutaneous dose of D-4517.2 (40 µg) significantly reduces CNV lesion area by~2-fold compared to vehicle control, which is consistent with previous observations and comparable with aflibercept efficacy.
  • A single oral dose of D-4517.2 (40 µg) also significantly reduces CNV lesion area and vascular leakage by ~2-fold. A 200 µg oral dose further reduces the CNV lesion area by ~3.5 fold.
  • These results suggest that oral administration of D-4517.2 has similar efficacy to aflibercept, and similar bioavailability when given orally or subcutaneously. This study supports the development of D-4517.2 as a potentially safe and effective oral agent for patients suffering from wet AMD or DME.

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,” in which he discussed the cellular localization and efficacy of D-4517.2 in a wet AMD mouse model.

Key highlights from poster presentation:

  • The study evaluated the localization of D-4517.2 in Vldr -/- knockout mice, an animal model with symptoms of type III wet AMD after birth.
  • Results indicated the nanomedicine conjugated with a fluorophore (D-Cy5) colocalized with activated microglia and macrophages within regions of ocular inflammation in Vldr-/-
  • Oral and subcutaneous administration of D-4517.2 significantly reduces the number of CNV lesions in Vldlr-/-mice suggesting a benefit of selectively inhibiting VEGFR in activated microglia/macrophages and RPE cells in the retina and choroid. The data further support that systemic administration of D-4517.2 is effective in reducing neovascular lesions associated with AMD and selectively targets activated microglia and macrophages.

About Wet AMD and DME  

Wet age-related macular degeneration (wet AMD) is a retinal disease that develops when abnormal blood vessels grow into the macula – a part of the retina at the back of the eye which is responsible for sharp central vision. These vessels leak blood or fluid which can lead to rapid loss of central vision. Wet AMD can be treated if caught early with drugs to stop the growth of the abnormal vessels. According to the World Health Organization, 196 million people have AMD globally, including 10.4 million people with moderate to severe vision impairment or blindness. Diabetic macular edema (DME) is a retinal disease that develops when there is an accumulation of fluid in the macula due to leaking blood vessels. DME is a result of diabetic retinopathy, a disease that damages the blood vessels in the retina which if left untreated builds pressure in the eye and leaks fluid. A recent study estimated approximately 100 million individuals suffer from DME globally.1 

About D-4517.2

D-4517.2 is a potent anti-angiogenic nanomedicine that crosses the blood-retinal barrier and selectively targets activated microglia, macrophages and hypertrophic retinal pigment epithelial cells in the eye. D-4517.2 has the potential to change the current treatment paradigm for neovascular age-related macular degeneration (wet AMD) and diabetic macular edema (DME) by offering an at-home dosing option by a subcutaneous route of administration rather than delivery via intravitreal injection (injection into the eye). D-4517.2 is in a Phase 2 clinical trial in patients with wet AMD or DME.  

About Ashvattha Therapeutics

Ashvattha Therapeutics is advancing a new class of clinical-stage nanomedicine therapeutics that transverse tissue barriers to selectively target activated cells only in regions of inflammation. Our targeted nanomedicine approach seeks to redefine precision medicine, empowering a new standard of care across ophthalmology, neurology, and inflammation. For more information, visit:

  1. Duphare C, Desai K, Gupta P, et al. Diabetic Macular Edema. [Updated 2023 Mar 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: 

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