• A single subcutaneous or oral dose of D-4517, a sunitinib analog, resulted in comparable or better inhibition of CNV to a single intravitreal (IVT) dose of aflibercept
• No observed toxicity at greater than 80 times the effective dose of D-4517
• Phase 1 study expected to be completed by year end, with initial Phase 2 data for D-4517 in wet AMD expected in mid-2022.

Ashvattha Therapeutics, a biotech company focused on novel hydroxyl dendrimer therapeutics (HDTs) targeting unmet medical needs in neuro-oncology, neurology and ophthalmology, today announced the presentation of a virtual poster supporting the development of its proprietary HDT, D-4517, for treatment of wet age-related macular disease (AMD) at the 2021 Association for Vision and Ophthalmology (ARVO) Annual Meeting, held virtually, May 1-7.

Details for the virtual poster are as follows:

Poster Title: Single Subcutaneous (or Oral) Dose of Anti-Angiogenesis Drug Safely Suppresses Choroidal Neovascularization Comparable to Intravitreal Aflibercept

Date / Time: Wednesday, May 5, 2021, 11:45 am – 1:30 pm PDT

Presenters: Jeffrey Cleland, et al.

Abstract Number: 3540583

“We are excited to present this preclinical proof of concept and toxicology data highlighting our lead candidate D-4517, a sunitinib analog, that utilizes our novel hydroxyl dendrimer (HD) technology at ARVO, one of the world’s leading ophthalmology conferences. Current treatments for wet AMD, a degenerative disease, require invasive, intravitreal injections into the eye, as often as once every 4 weeks. Our results show that a single subcutaneous or oral dose of D-4517 safely suppresses choroidal neovascularization, a major cause of vision loss, comparable to intravitreal aflibercept. A Phase 1 study is expected to be completed by year end, with initial Phase 2 data in wet AMD patients expected in mid-2022,” said Jeffrey Cleland, Ph.D., Chairman, CEO & President at Ashvattha Therapeutics.

Hydroxyl dendrimers (HDs) selectively target choroidal neovascular (CNV) lesions after a single systemic dose. CNV involves the growth of new blood vessels that originate from the choroid through a break in the Bruch membrane into the sub–retinal pigment epithelium or subretinal space. CNV is a major cause of visual loss. HDs are taken up by macrophages, microglia and hypertropic retinal pigment epithelial (RPE) cells. HDs are retained in these cells in CNV lesion for at least 1 month after a single systemic dose. Sunitinib has been shown to suppress neovascularization in animals and humans, but has significant off target toxicity when administered systemically.

Covalently linking a sunitinib analog to the HD creates a new chemical entity that solves the toxicity issues while retaining potency. Previous studies demonstrated a sustained inhibition (14 days) of CNV formation after a single systemic dose of HD-sunitinib analog (D-4517) comparable to an intravitreal (IVT) dose of aflibercept.

Based on results from this preclinical study, a single subcutaneous or oral dose of D-4517 resulted in comparable or better inhibition of CNV to a single IVT aflibercept dose at the same total mass. Repeat dose (12 mg/kg daily) or high single dose (167 mg/kg) of D-4517 did not result in any observed adverse effects in rats, whereas a comparable dose of sunitinib caused significant toxicity and mortality. There was no observed toxicity at >80 fold higher dose than effective dose in preclinical studies. The lack of toxicity is the result of D-4517 renal clearance with no significant exposure to the liver or detectable metabolism as observed with other clinical stage HDTs.

About Ashvattha Therapeutics

Ashvattha Therapeutics, a clinical-stage biopharmaceutical company, is developing novel therapeutics that target and alter specific cells in areas of diseased tissues. The Company’s targeted platform technology, hydroxyl dendrimers (HD), is exclusively licensed from Johns Hopkins University. HDs chemically conjugated to disease modifying drugs create novel proprietary HD therapeutics (HDTs). Ashvattha has initiated multiple programs with HDTs focused on neuro-oncology, neurology, age-related macular degeneration (AMD), and hyperinflammation in diseases such as COVID-19. For more information, visit: www.avttx.com.

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