July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Chronic Nonclinical Ocular Toxicity Study of KSI-301 Demonstrates Tolerability after Intravitreal Administration in Cynomolgus Monkeys
Author Affiliations & Notes
  • John Sinclair
    Kodiak Sciences Inc., Palo Alto, California, United States
  • hong liang
    Kodiak Sciences Inc., Palo Alto, California, United States
  • zachary antonio
    Covance Laboratories Inc., Wisconsin, United States
  • paul miller
    OSOD, LLC, Wisconsin, United States
  • avery tolosa
    Kodiak Sciences Inc., Palo Alto, California, United States
  • joel naor
    Kodiak Sciences Inc., Palo Alto, California, United States
  • leah quarberg
    Covance Laboratories Inc., Wisconsin, United States
  • alok sharma
    Covance Laboratories Inc., Wisconsin, United States
  • Xiaojian Huang
    Kodiak Sciences Inc., Palo Alto, California, United States
  • Janine Lu
    Kodiak Sciences Inc., Palo Alto, California, United States
  • William Ngo
    Kodiak Sciences Inc., Palo Alto, California, United States
  • dan dang
    Kodiak Sciences Inc., Palo Alto, California, United States
  • frances clemo
    Covance Laboratories Inc., Wisconsin, United States
  • James N Ver Hoeve
    OSOD, LLC, Wisconsin, United States
  • T. Michael Nork
    OSOD, LLC, Wisconsin, United States
  • D. Victor Perlroth
    Kodiak Sciences Inc., Palo Alto, California, United States
  • Footnotes
    Commercial Relationships   John Sinclair, Kodiak Sciences Inc. (E); hong liang, Kodiak Sciences Inc. (E); zachary antonio, Covance Laboratories Inc. (E); paul miller, OSOD, LLC (E); avery tolosa, Kodiak Sciences Inc. (E); joel naor, Kodiak Sciences Inc. (E); leah quarberg, Covance Laboratories Inc. (E); alok sharma, Covance Laboratories Inc. (E); Xiaojian Huang, Kodiak Sciences Inc. (E); Janine Lu, Kodiak Sciences Inc. (E); William Ngo, Kodiak Sciences Inc. (E); dan dang, Kodiak Sciences Inc. (E); frances clemo, Covance Laboratories Inc. (E); James Ver Hoeve, OSOD, LLC (E); T. Michael Nork, OSOD, LLC (E); D. Victor Perlroth, Kodiak Sciences Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 126. doi:https://doi.org/
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      John Sinclair, hong liang, zachary antonio, paul miller, avery tolosa, joel naor, leah quarberg, alok sharma, Xiaojian Huang, Janine Lu, William Ngo, dan dang, frances clemo, James N Ver Hoeve, T. Michael Nork, D. Victor Perlroth; Chronic Nonclinical Ocular Toxicity Study of KSI-301 Demonstrates Tolerability after Intravitreal Administration in Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2019;60(9):126. doi: https://doi.org/.

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

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Abstract

Purpose : KSI-301, a novel antibody biopolymer conjugate that inhibits VEGF, is currently in clinical development for the treatment of retinal vascular diseases. The toxicity of repeated intravitreal (IVT) administration of KSI-301 in non-human primates to inform further clinical development was evaluated.

Methods : Male and female cynomolgus monkeys were administered KSI-301 (2.5 or 5 mg/eye bilaterally) or vehicle via IVT injection at 4-week intervals (Q4W) for a total of 7 doses over the 26-week dosing period. For an additional 14 weeks, two recovery groups (vehicle and 5 mg/eye) were assessed for reversibility of treatment related effects. Assessment of toxicity was based on clinical and ophthalmic observations, intraocular pressure (IOP), optical coherence tomography (OCT), fundus ocular photography (FP), electroretinography (ERG), body weight, qualitative food consumption, and clinical and anatomic pathology.

Results : Following 7 doses Q4W, treatment with up to 5 mg/eye/dose IVT KSI-301 was generally well tolerated. There were no KSI-301 related alterations in body weight or weight gain, effects on clinical pathology parameters, macroscopic observations, or organ weight parameters. KSI-301 treatment was associated with dose-related, transient low-grade aqueous and vitreous cell that peaked shortly after dosing and subsided prior to the next dose. There were correlating microscopic findings in the ciliary body and vitreous, however, these were not clearly dose related and were attributed to an immune response consistent with observations of other humanized biologics in non-human primates. Other findings, such as transient aqueous flare and non-inflammatory diffuse hazy vitreous, were likely attributable to the physical features of the test article formulation (e.g. Tyndall effect). No KSI-301 related abnormalities were noted for IOP, OCT, FP, or ERG.

Conclusions : Repeated bilateral IVT administration of KSI-301 up to 5 mg/eye/dose (the maximum feasible dose) in cynomolgus monkeys was safe and well tolerated. These results provide a clear margin of safety for repeat dosing and information for adequate safety monitoring to support further clinical investigations.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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