Intraocular pressure is comprised of four distinct components that, combined, lead to total intraocular pressure (IOP). These four components are currently best described by the modified Goldmann equation, which includes contributions from the Aqueous Humor Inflow Rate (Q), Uveoscleral Outflow Rate (U), Conventional Outflow Facility (C), and Episcleral Venous Pressure (EVP). EVP is the largest component of IOP, contributing around 2/3 of total IOP. However, no approved therapy to date solely targets EVP.
Modified Goldmann Equation for IOP
Aqueous Humor Inflow Rate
- Timolol
- Betaxolol
- Levobunolol
- Metipranolol
- Brimonidine
- Apraclonidine
- Brinzolamide
- Dorzolamide
- Acetazolamide
- Methazolamide
Uveoscleral Outflow Rate
- Latanoprost
- Bimatoprost
- Travaprost
- Tafluprost
- Latanoprostene bunod
- Brimonidine
- Apraclonidine
Conventional Trabecular Outflow Facility
- Pilocarpine
- Carbachol
- Netarsudil
Episcleral Venous Pressure
Specifically targeted by QLS-101
Our Pipeline
Discovery | Pre-clinical | IND-Enabling | Phase 1 | Phase 2 | Phase 3 | Approval | |
---|---|---|---|---|---|---|---|
QLS-101*POAG/OHT | Phase 2 | ||||||
QLS-101*NTG | Phase 1 | ||||||
QLS-101*SWS | Phase 1 | ||||||
QLS-700SR-IOP | Discovery | ||||||
QLS-700Neuroprotection | Discovery |
QLS-101
QLS-101 is our lead program based upon research from the laboratory of Professor Michael Fautsch at Mayo Clinic. The original compounds were first synthesized at the laboratory of Professor Peter Dosa at the University of Minnesota.
QLS-101 is a novel prodrug of a well-characterized ATP-sensitive potassium (KATP) channel modulator that lowers intraocular pressure (IOP) by relaxing vessels of the vascular and vascular-like tissues distal to the Trabecular Meshwork, thereby reducing distal outflow resistance and lowering Episcleral Venous Pressure (EVP).
Though multiple mechanisms of action exist to lower IOP in patients with glaucoma, these agents all target only 3 of the 4 components of IOP as described by the Goldmann equation for IOP: the Aqueous Humor Inflow Rate (Q), Uveoscleral Outflow Rate (U), or Conventional Outflow Facility (C). There are currently no approved drugs that solely target the reduction of EVP. This leaves a significant gap in the potential to maximally lower IOP since EVP can be the largest determinant of overall IOP.
QLS-101 has shown efficacy in lowering IOP across multiple preclinical animal species, including mice, rabbits, dogs, and non-human primates, as well as in human eye explants. To date, QLS-101 has been demonstrated to be well-tolerated with no observed hyperemia in the efficacious dose range.
By uniquely targeting EVP and distal outflow, QLS-101 enables the treatment of diseases for which there are currently inadequate therapies: namely, those diseases of pathologic EVP or where EVP currently sets the floor for maximal therapy despite the use of multiple agents since no approved drugs currently lower EVP primarily.
Qlaris Bio has initiated clinical studies with QLS-101 in patients with Primary Open Angle Glaucoma, Ocular Hypertension, Normal Tension Glaucoma, and Sturge-Weber syndrome.