July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Topical or Subcutaneous Administration of AKB-9778, a Tie2 Activator, Reduces IOP in NZW Rabbits
Author Affiliations & Notes
  • Glenwood G Gum
    Absorption Systems, San Diego, California, United States
  • John Janusz
    Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
  • Brandi Soldo
    Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
  • Brian Walker
    Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
  • Akshay Buch
    Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
  • Steve Pakola
    Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
  • Kevin G Peters
    Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
  • Footnotes
    Commercial Relationships   Glenwood Gum, None; John Janusz, Aerpio Pharmaceuticals (E); Brandi Soldo, Aerpio Pharmaceuticals (E); Brian Walker, Aerpio Pharmaceuticals (E); Akshay Buch, Aerpio Pharmaceuticals (E); Steve Pakola, Aerpio Pharmaceuticals (E); Kevin Peters, Aerpio Pharmaceuticals (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2719. doi:
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      Glenwood G Gum, John Janusz, Brandi Soldo, Brian Walker, Akshay Buch, Steve Pakola, Kevin G Peters; Topical or Subcutaneous Administration of AKB-9778, a Tie2 Activator, Reduces IOP in NZW Rabbits. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2719.

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

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Abstract

Purpose : Tie2 dysfunction in the conventional outflow pathway has been implicated in glaucoma (Kim et al, JCI 2017; 127:3877-96). AKB-9778 is a small molecule inhibitor of VE-PTP, the most critical negative regulator of Tie2. The purpose of the study was to test the tolerability and effect on intraocular pressure (IOP) of repeat administration of AKB-9778 in normotensive New Zealand White(NZW) rabbits.

Methods : Twenty-five female NZW rabbits (5 per treatment group) were administered AKB-9778 for seven days topically (15 or 40 mg/ml 30 µl per eye) once or twice daily into both eyes, vehicle twice daily to both eyes, or 10 mg/kg twice daily subcutaneously (SC). IOP was measured daily at baseline prior to dosing, on each day of dosing, and 24 hours after the last dose. Slit-lamp ophthalmic examinations were performed on the first and fourth day of dosing and the day after dosing ended. General health observations were performed daily.

Results : AKB-9778 40 mg/ml topically administered either QD or BID reduced IOP, whereas the 15 mg/ml BID topical dose and the 10 mg/kg SC dose were not as effective (Figure 1). Area under the curve (AUC) of IOP values during the study showed a statistically significantly lower IOP for 40 mg/ml QD and BID groups compared to the vehicle group (p<0.01 and <0.05, respectively). IOP reductions persisted through the last assessment 24 hours after the end of dosing (Figure 1).
No adverse effects of the test article on general health were seen during the study. Mild conjunctival congestion, observed in a minority of animals, appeared to be unrelated to the test article, as this finding was also observed in the vehicle group and decreased with repeated dosing.

Conclusions : Topical administration of the Tie2 activator AKB-9778 was well tolerated and reduced IOP in rabbits. These findings support evaluation of Tie2 activation by AKB-9778 as a potential approach for IOP reduction in patients with open angle glaucoma or ocular hypertension.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1 - Day 7 (End of Treatment) and Day 8 (24 hrs after last dose) Vehicle-corrected IOP by Treatment Group

Figure 1 - Day 7 (End of Treatment) and Day 8 (24 hrs after last dose) Vehicle-corrected IOP by Treatment Group

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