Qlaris Bio, Inc. announced a new clinical plot twist this week—the company is developing a novel, preservative-free (PF), fixed-dose combination (FDC) therapy incorporating its lead asset (QLS-111) and latanoprost.
Its intent: To treat glaucoma.
First, a refresher on Qlaris.
Headquartered in Massachusetts, the clinical-stage biotech company’s therapeutic pipeline is targeted toward treating ophthalmic diseases with unmet needs—with a particular emphasis on glaucoma and ocular hypertension (OHT).
Zeroing in on these unmet needs, Qlaris identified three key areas to gear its approach toward:
- New mechanisms of action (MOA) to enable treatment of glaucoma’s “unique aspects” not addressed by current therapies on the market
- Therapies, with a sustained duration of action, that reduce eye drop burden and control IOP fluctuation on a daily basis
- Novel neuroprotective therapies operating independently from IOP-lowering meds to protect the optic nerve and preserve vision
Next up: QLS-111.
Under clinical development to address that first unmet area (a new MOA for glaucoma), QLS-111 is an investigational eye drop intended to lower intraocular pressure (IOP).
How: By reducing episcleral venous pressure (EVP)—a major detriment of IOP that leads to glaucoma—via a MOA that widens the blood vessels to enable blood to flow more easily throughout the body (a process referred to as “vasodilatory”).
And what does this EVP lowering do, exactly?
Quite simply: It also lowers IOP.
How this is done: By QLS-111 relaxing vessels of the vascular and vascular-like tissues distal to the trabecular meshwork (TM), leading to reduced distal outflow resistance and a lowering of EVP.
And the players that enable this: That would be adenosine triphosphate-sensitive potassium (KATP) channel modulators, which improve outflow—via distal vascular tissues of the eye—to reduce IOP.
- Take note: KATP channel modulators usually treat conditions such as type 2 diabetes by opening or closing KATP channels.
What’s the clinical data on it so far?
Earlier this year, Qlaris reported positive findings from two phase 2 clinical trials evaluating the asset for both primary open-angle glaucoma (POAG) and OHT.
What to know about those trials’ setup: Patients were randomized to receive either latanoprost alone or or latanoprost with one of three different QLS-111 doses, with twice daily (BID) dosings.
- Why latanaprost: This prostaglandin analogue (PGA) is a common first-line treatment for lowering IOP in glaucoma—and was the first to be FDA-approved for ocular use (in 1996).
And in regards to those findings?
Both studies demonstrated that the 0.015% QLS-111 concentration (the lowest dose) + latanoprost resulted in the greatest IOP decrease.
- QLS-111 achieved over 3 mmHg of additional IOP reduction versus latanprost alone
See here for more data on both studies.
Good to know … and now to this new FDC.
Dubbed QLS-111-FDC, the formulation is under development to treat patients diagnosed with:
- POAG
- Normal-tension glaucoma (NTG)
- OHT
More specifically: These patients are those for whom optimal iOP control “may be unachievable due to the need to lower (EVP).”
Why hone in on EVP control?
The main reason: EVP management is reported to be the only component of IOP that has yet to be addressed and managed by current FDA-approved treatments in the U.S market.
And the thought behind this new combination?
Qlaris shared that these two agents—QLS-111 and latanoprost—offer a “complementary dual mechanism approach aimed to further enhance IOP control.”
Even further: As evidenced by that recent phase 2 data—which also demonstrated additional IOP reduction without any development of hyperemia or other adverse events—QLS-111-FDC has the potential to improve IOP control "without compromising safety or tolerability."
Nice! So what’s next for the new asset?
Outside of announcing this combination, the company divulged no specific clinical plans.
However, we’re likely to hear more on what to anticipate (potentially a clinical trial evaluating this?) in the near future.