June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Ocular distribution and exposure of AU-011 after suprachoroidal or intravitreal administration in an orthotopic rabbit model of human uveal melanoma
Author Affiliations & Notes
  • Anneli Savinainen
    Aura Biosciences, Cambridge, Massachusetts, United States
  • Hans E Grossniklaus
    Emory Eye Care Center, Atlanta, Georgia, United States
  • Shin King
    Emory Eye Care Center, Atlanta, Georgia, United States
  • Joan Wicks
    Stage Bio, Mt Jackson, Virginia, United States
  • Cadmus C Rich
    Aura Biosciences, Cambridge, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Anneli Savinainen, Aura Biosciences (E); Hans Grossniklaus, None; Shin King, None; Joan Wicks, None; Cadmus Rich, Aura Biosciences (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2861. doi:
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      Anneli Savinainen, Hans E Grossniklaus, Shin King, Joan Wicks, Cadmus C Rich; Ocular distribution and exposure of AU-011 after suprachoroidal or intravitreal administration in an orthotopic rabbit model of human uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2861.

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

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Abstract

Purpose : The aim of this study was to compare the ocular distribution and exposure, after suprachoroidal (SC) and intravitreal (IVT) administration of AU-011 in a rabbit model of human uveal melanoma. AU-011 (belzupacap sarotalocan) is designed to be a highly tumor targeted treatment for uveal melanoma that causes acute cellular necrosis with pro-immunogenic cell death, which triggers a secondary immune response. AU-011 has shown promising preliminary results in a Phase 1b/2 clinical trial for primary choroidal melanoma delivered by IVT administration. A Phase 2 clinical trial is ongoing to evaluate SC administration.

Methods : Human uveal melanoma 92.1 cells were implanted in the choroid of rabbit eyes. Once tumors reached ~5mm in basal diameter, AU-011 was administered by SC or IVT injection. Ocular tissues including tumor samples were taken at multiple time points up to 48 hours post injection. The bioanalytical method for exposure in vitreous, choroid/retina and tumor were based on an electrochemiluminescence immunoassay. Distribution of AU-011 in the tumor was evaluated by immunohistochemical staining using a monoclonal rat antibody against the virus-like particle component of AU-011.

Results : After SC administration, we observed negligible levels of AU-011 in the vitreous and high exposure levels in the tumor and choroid/retina. The exposure remained high in the tumor up to 48 hours post injection for both routes of administration. The exposure of AU-011 in the tumor was approximately 5x higher when AU-011 was administered by SC injection compared to IVT injection. Mean concentrations were 12459 +/- 5190 and 1996 +/- 421 ng/mL, respectively. Positive IHC staining support that AU-011 was present in the tumor after both SC and IVT administration. AU-011 staining was observed penetrating throughout the tumor in the SC injected group whereas AU-011 staining in the IVT injected eyes demonstrated that AU-011 was mostly localized on the apex or vitreal surface of the tumor.

Conclusions : These data suggest that SC administration is superior to IVT administration with an improved tumor distribution, higher tumor bioavailability and less unintended exposure in the vitreous and other key ocular structures, which may result in an improved therapeutic index. AU-011 is currently being evaluated in two clinical trials, one with SC and one with IVT administration.

This is a 2021 ARVO Annual Meeting abstract.

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