June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Preclinical evaluation of RTC-1119, a surface eroding intracameral implant composed entirely of a latanoprost acid prodrug, for long-term intraocular pressure control
Author Affiliations & Notes
  • Ike Ahmed
    Department of Ophthalmology and Visual Sciences, University of Utah Health, Salt Lake City, Utah, United States
    Department of Ophthalmology, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada
  • Kyle Battiston
    Ripple Therapeutics, Ontario, Canada
  • Shadi Taghavi
    Ripple Therapeutics, Ontario, Canada
  • Hans Fischer
    Ripple Therapeutics, Ontario, Canada
  • Emily Baldwin
    Ripple Therapeutics, Ontario, Canada
  • Matthew Statham
    Ripple Therapeutics, Ontario, Canada
  • Jonathan Day
    Ripple Therapeutics, Ontario, Canada
  • Adam Daley
    Ripple Therapeutics, Ontario, Canada
  • Ben Muirhead
    Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Emily Anne Hicks
    Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Jennifer Jing Yuan Tian
    Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Heather Sheardown
    Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Ian Parrag
    Ripple Therapeutics, Ontario, Canada
  • Wendy Naimark
    Ripple Therapeutics, Ontario, Canada
  • Footnotes
    Commercial Relationships   Ike Ahmed Ripple Therapeutics, Code C (Consultant/Contractor), Aequus, Code C (Consultant/Contractor), Aerie, Code C (Consultant/Contractor), Akorn, Code C (Consultant/Contractor), Aquea Health, Inc, Code C (Consultant/Contractor), ArcScan, Code C (Consultant/Contractor), Alcon, Code R (Recipient), Allergan, Code R (Recipient); Kyle Battiston Ripple Therapeutics, Code E (Employment); Shadi Taghavi Ripple Therapeutics, Code E (Employment); Hans Fischer Ripple Therapeutics, Code E (Employment); Emily Baldwin Ripple Therapeutics, Code E (Employment); Matthew Statham Ripple Therapeutics, Code E (Employment); Jonathan Day Ripple Therapeutics, Code E (Employment); Adam Daley Ripple Therapeutics, Code E (Employment); Ben Muirhead None; Emily Anne Hicks None; Jennifer Tian None; Heather Sheardown None; Ian Parrag Ripple Therapeutics, Code E (Employment); Wendy Naimark Ripple Therapeutics, Code E (Employment)
  • Footnotes
    Support  NSERC Alliance ALLRP 556570 - 20
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 442. doi:
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      Ike Ahmed, Kyle Battiston, Shadi Taghavi, Hans Fischer, Emily Baldwin, Matthew Statham, Jonathan Day, Adam Daley, Ben Muirhead, Emily Anne Hicks, Jennifer Jing Yuan Tian, Heather Sheardown, Ian Parrag, Wendy Naimark; Preclinical evaluation of RTC-1119, a surface eroding intracameral implant composed entirely of a latanoprost acid prodrug, for long-term intraocular pressure control. Invest. Ophthalmol. Vis. Sci. 2022;63(7):442.

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

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Abstract

Purpose : Sustained release implants composed entirely from novel prodrugs have the potential to improve the safety and compliance of ophthalmic medications. The prodrug implants are non-swelling, exhibit surface erosion-based drug release, and avoid polymer-associated pro-inflammatory degradation products. The purpose of this work was to evaluate the preclinical ocular safety and pharmacokinetics of a prostaglandin prodrug intracameral implant (RTC-1119 IC implant) with >6 mo sustained release of latanoprost acid for primary open angle glaucoma and ocular hypertension.

Methods : RTC-1119 IC Implants were prepared by extrusion of RTC-1119, a prodrug of latanoprost acid, without the inclusion of a polymer carrier. Tolerability and surface erosion of RTC-1119 IC Implants was evaluated following IC administration in New Zealand white rabbits (4 rabbits, 7 eyes) for a duration of 7.5 months. Implants were visualized by gonioscopy. Safety was assessed through ocular exams, anterior segment optical coherence tomography, and histopathology. Quantification of latanoprost acid in aqueous humor and iris-ciliary body was assessed by liquid chromatography-mass spectrometry (Days 7, 28).

Results : The RTC-1119 IC Implant was well tolerated, with ocular exams indicating no adverse findings. No change in corneal thickness or implant associated inflammation was observed. Gonioscopy showed implants becoming smaller in diameter over time, supporting the surface erosion mechanism of drug release, and completely biodegrade without leaving behind any remnants due to the absence of a carrier system (Figure 1). Consistent levels of latanoprost acid were observed in the aqueous humor and iris-ciliary body at Day 7 and Day 28 (Figure 2).

Conclusions : The present study indicates that the RTC-1119 IC Implant is well tolerated in the rabbit eye, where it undergoes surface erosion to provide controlled release of latanoprost acid. Gonioscopic visualization of implants indicate that duration of drug release is >6 mo. Ongoing work is evaluating the IOP lowering effect of the RTC-1119 IC Implant in a canine model. This data supports the further development of the RTC-1119 IC Implant towards first-in-human clinical trials.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1 Gonioscopic visualization of RTC-1119 IC Implants (white arrows).

Figure 1 Gonioscopic visualization of RTC-1119 IC Implants (white arrows).

 

PK of RTC-1119 IC Implant in rabbit eyes compared to latanoprost eyedrops.

PK of RTC-1119 IC Implant in rabbit eyes compared to latanoprost eyedrops.

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