June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Systemic and Ocular Toxicology and Pharmacokinetic Profiles of QLS-101, a Novel Topical IOP-Lowering Therapeutic
Author Affiliations & Notes
  • Barbara M Wirostko
    Qlaris Bio, Inc, Massachusetts, United States
    University of Utah Health John A Moran Eye Center, Salt Lake City, Utah, United States
  • Hemchand K. Sookdeo
    Qlaris Bio, Inc, Massachusetts, United States
  • Thurein Htoo
    Qlaris Bio, Inc, Massachusetts, United States
  • Ralph Casale
    Qlaris Bio, Inc, Massachusetts, United States
  • Uttio Roy Chowdhury
    Ophthalmology, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Michael P Fautsch
    Ophthalmology, Mayo Clinic Minnesota, Rochester, Minnesota, United States
    Qlaris Bio, Inc, Massachusetts, United States
  • Cynthia Steel
    Qlaris Bio, Inc, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Barbara Wirostko, Qlaris Bio, Inc (E), Qlaris Bio, Inc (I), Qlaris Bio, Inc (P), Qlaris Bio, Inc. (S); Hemchand K. Sookdeo, Qlaris Bio, Inc (I), Qlaris Bio, Inc (E), Qlaris Bio, Inc. (E); Thurein Htoo, Qlaris Bio, Inc (E), Qlaris Bio, Inc (P), Qlaris Bio, Inc (S), Qlaris Bio, Inc. (I); Ralph Casale, Qlaris Bio, Inc (E), Qlaris Bio, Inc. (I); Uttio Roy Chowdhury, Qlaris Bio, Inc (F), Qlaris Bio, Inc. (R); Michael Fautsch, Qlaris Bio, Inc (I), Qlaris Bio, Inc (S), Qlaris Bio, Inc. (P); Cynthia Steel, Qlaris Bio, Inc (E), Qlaris Bio, Inc. (I)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2754. doi:
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      Barbara M Wirostko, Hemchand K. Sookdeo, Thurein Htoo, Ralph Casale, Uttio Roy Chowdhury, Michael P Fautsch, Cynthia Steel; Systemic and Ocular Toxicology and Pharmacokinetic Profiles of QLS-101, a Novel Topical IOP-Lowering Therapeutic. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2754.

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

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Abstract

Purpose : QLS-101, a water-soluble phosphate ester prodrug of an ATP-sensitive potassium channel opener, is being developed by Qlaris Bio as an ocular hypotensive agent with a novel mode of action that affects distal outflow resistance and episcleral venous pressure. This summarizes the potential toxicity and pharmacokinetic (PK) profiles of QLS-101 in beagle dogs.

Methods : To assess ocular toxicity and PK, beagle dogs (age 5-7 months) were dosed topically (OU) once daily for 28 days with 2.0%, 4.0%, or 8.0% QLS-101 (n=3 males and 3 females per group). To evaluate systemic maximum tolerated dose (MTD), single escalating doses of QLS-101 (0.05-5.0 mg/kg/day) were administered by i.v. bolus to one male and one female beagle dog, with a 48h minimum observation period between doses. Plasma samples were collected at various timepoints in both studies, concentrations of QLS-101 and its active moiety QLS-100 were determined by LC/MS-MS, and data used to generate PK parameters. Mortality, clinical observations, body and organ weights, and food consumption were assessed in each study. Necropsy examinations were performed and select tissues were isolated and prepared for histopathology.

Results : QLS-101 was well-tolerated at all dose levels except 5 mg/kg/day i.v. When dosed topically, the no-observed-adverse-effect level (NOAEL) was determined to be 8.0%. At this dose, the mean Cmax and AUC Tlast values on day 28 were 147 ng/mL and 1.26 ug*h/ml, respectively, for males, with similar results in females. QLS-100 Cmax and AUC Tlast levels at NOAEL were 31 ng/ml and 166 ng*h/ml in males, with similar results in females. Using dogs administered single escalating i.v. doses, the MTD was determined to be 3 mg/kg. Side effects were limited to non-adverse skin redness at all dose levels, consistent with vasodilation. Unexpectedly, the observed skin redness initially presented peripherally in the distal limbs (fore and hindpaws) and in the pinnae rather than the trunk, neck, or faceThe MTD corresponded to sex-combined Cmax and AUCTlast values of 16.4 μg/mL and 106.55 μg*h/mL for QLS-101, and 35.5 ng/mL and 431 ng*h/mL, for QLS-100. No mortality, change in body weight or food consumption were noted. Histological examination showed no systemic toxicity as a result of QLS-101 treatment.

Conclusions : QLS-101 is well-tolerated in beagle dogs and suitable for clinical development as an IOP-lowering therapeutic.

This is a 2021 ARVO Annual Meeting abstract.

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