June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Preclinical Pharmacokinetics of VRDN-003, A Next-Generation Half-life Extended Antibody to the IGF-1 Receptor for Thyroid Eye Disease
Author Affiliations & Notes
  • Brent Dickinson
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Kelly Foster
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Vahe Bedian
    Viridian Therapeutics Inc, Waltham, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Brent Dickinson Viridian Therapeutics Inc., Code E (Employment), Viridian Therapeutics Inc., Code I (Personal Financial Interest); Kelly Foster Viridian Therapeutics Inc., Code E (Employment), Viridian Therapeutics Inc., Code I (Personal Financial Interest); Vahe Bedian Viridian Therapeutics Inc., Code E (Employment), Viridian Therapeutics Inc., Code I (Personal Financial Interest), Viridian Therapeutics Inc., Code P (Patent)
  • Footnotes
    Support  Study funded by Viridian Therapeutics Inc.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4043. doi:
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    • Get Citation

      Brent Dickinson, Kelly Foster, Vahe Bedian; Preclinical Pharmacokinetics of VRDN-003, A Next-Generation Half-life Extended Antibody to the IGF-1 Receptor for Thyroid Eye Disease. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4043.

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

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Abstract

Purpose : Clinical and preclinical studies have demonstrated IGF-1 receptor (IGF-1R) antagonism reduces the inflammation and proptosis that occur in thyroid eye disease (TED). VRDN-001 is a full antagonist to IGF-1R with subnanomolar affinity, while VRDN-003 is a next-generation, half-life extended version of VRDN-001 designed to enable subcutaneous administration via a fixed dose patient-controlled pen. We compared the pharmacokinetic (PK) parameters of VRDN-003 with those of VRDN-001 in non-human primates.

Methods : VRDN-001 and VRDN-003 were administered to cynomolgus monkeys as a single dose by either intravenous (IV) infusion or subcutaneous (SC) injection at 7.5 mg/kg. PK samples were collected at 12 time points (VRDN-001 group) or 15 time points (VRDN-003 group). Data were analyzed using the WinNonlin non-compartmental model.

Results : When administered via either IV infusion or SC injection, half-life was approximately two times as long, AUCinf approximately 65% greater, and clearance approximately 40% less for VRDN-003 vs VRDN-001 (Table 1). Bioavailability (ratio AUC-SC/AUC-IV) was similar for the two antibodies: 71% for VRDN-003 and 70% for VRDN-001.

Conclusions : VRDN-003 demonstrated a desirable PK profile in non-human primates, with approximately twice the half-life of first generation anti-IGF-1R antibodies, suggesting potential for convenient, low-volume, SC self-administration for TED patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Table 1. IV and SC PK Parameters of VRDN-001 and VRDN-003

Table 1. IV and SC PK Parameters of VRDN-001 and VRDN-003

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