July 2019
Volume 60, Issue 9
ARVO Annual Meeting Abstract  |   July 2019
The discovery of novel LFA-1 antagonist VVN001 to treat Dry Eye Disease (DED)
Author Affiliations & Notes
  • Yong Li
    VivaVision Biotech Inc, China
  • Erning Xia
    VivaVision Biotech Inc, China
  • wang shen
    VivaVision Biotech Inc, China
  • Footnotes
    Commercial Relationships   Yong Li, None; Erning Xia, None; wang shen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 293. doi:
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    • Get Citation

      Yong Li, Erning Xia, wang shen; The discovery of novel LFA-1 antagonist VVN001 to treat Dry Eye Disease (DED). Invest. Ophthalmol. Vis. Sci. 2019;60(9):293.

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

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Purpose :
The research aims at discovering second generation cell adhesion molecule LFA-1 antagonist. The new LFA1 antagonist would have lower dosing frequency (patient compliance), less irritation upon instillation, and less other side effect such as dysgeusia (bad taste).

Methods :
Structure-activity-relationship (SAR) studies were used to optimize a series phosphorus containing molecules into potent LFA-1 antagonists. Cellular assay of inhibition of Jurkat cell adhesion to ICAM-1 was used as the primary assay. Rabbit ocular pharmacokinetics, and mouse dry eye model are used to evaluate the molecules in vivo. Physicochemical properties and novel structures are also optimized during the process.

Results :
A highly potent, novel LFA-1 antagonist VVN001 is identified: Jurkat cell adhesion IC50 is < 10 nM.
High concentration of the drug is found in cornea and conjunctiva tissues 24 hours after instillation of one drop 5% solution of drug to rabbit eyes. Specifically, >500 folds of IC50 in conjunctiva, and >100 folds of IC50 in cornea. These data indicate that once daily application of the new eye drop drug will be sufficient to treat dry eye disease.
The novel new LFA-1 inhibitor also exhibits high water solubility (>10% aqueous solubility at pH 7.4), indicating potential less side when instilled into eyes.
Mouse dry eye model indicates that the new novel LFA-1 antagonist VVN001 is more effective in treating dry eye disease than lifitegrast

Conclusions :
A novel LFA-1 antagonist VVN001 is identified, which is potentially better than lifitegrast. The new drug VVN001 is currently under IND enabling studies, and is expected to enter clinical trials in late 2019.

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


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