June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
AXT107 an Inhibitor of Neovascularization, Vascular Leakage, and Inflammation, Is Well-Tolerated and Could Potentially Be Dosed Once a Year to Treat Retinal Vascular Diseases
Author Affiliations & Notes
  • Niranjan Pandey
    AsclepiX Therapeutics, Baltimore, Maryland, United States
    Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Niranjan Pandey, AsclepiX Therapeutics (E)
  • Footnotes
    Support  NIH Grant R44EY027632
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3304. doi:
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      Niranjan Pandey; AXT107 an Inhibitor of Neovascularization, Vascular Leakage, and Inflammation, Is Well-Tolerated and Could Potentially Be Dosed Once a Year to Treat Retinal Vascular Diseases. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3304.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To assess the safety and pharmacokinetics (PK) of AXT107, a synthetic 20-mer peptide that blocks VEGF receptor 2 and activates Tie2, in preclinical studies.

Methods : Safety, PK, and ocular tissue distribution of 100, 250, 500, and 1000 µg of AXT107 injected intravitreally were tested in rabbit and minipig. GLP safety was studied over 9 months and PK and ocular tissue distribution were tested in rabbit and minipig for 15 months and 9 months respectively. Mass spectrometry was used to quantify AXT107 in plasma, aqueous humor, vitreous humor, retina, and choroid-RPE

Results : AXT107 was well tolerated in rabbit and minipig for 9 months after a single intravitreal administration of all doses of AXT107 in GLP studies. No increase in intraocular pressure, no inflammation, and no changes in ERG were observed throughout the 9-month period in both species. Within a few minutes of administration of a liquid formulation of AXT107, it formed a gel, whose size and appearance were dose-dependent, in the vitreous. The gel was compact and remained below the visual axis over the observation period. AXT107 was quantifiable in the gel by mass spectrometry and found to decrease over the duration of the study in both species. AXT107 was found at efficacious levels on the retina and choroid-RPE and at low levels in the bulk vitreous, and below levels of quantitation (BLQ) in the aqueous humor and other ocular tissues. AXT107 levels were also BLQ in plasma over the duration of the studies in both species. The levels of AXT107 in the retina and choroid were comparable at all doses of AXT107 tested. The half-life of the gel in the vitreous was found to be about 180 days.

Conclusions : Multiple doses of a single injection of AXT107 injected intravitreally were found to be safe and well-tolerated in GLP safety studies over 9-months in two species. PK and ocular distribution studies in rabbit and minipig showed that AXT107 formed a gel upon intravitreal injection that stayed below the visual axis releasing AXT107 slowly over the course of the study with a half-life of 180 days. The released AXT107 was found to be present at efficacious levels in the retina and choroidal tissues. These studies suggest that AXT107 is safe for intravitreal injection and support potentially once a year dosing in the clinic.

This is a 2021 ARVO Annual Meeting abstract.

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