New findings from a phase 3b exploratory trial indicate favorable outcomes for Nicox SA’s NCX 470, under clinical investigation to treat patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
I need a refresher on NCX 470.
Most notably: NCX 470 is Nicox’s lead asset.
What it is: A novel nitric oxide (NO)-donating bimatoprost formulation that features intraocular pressure (IOP)-lowering effects of NO and prostaglandin analogs (PGAs; long considered a first-line [and branded] treatment for glaucoma).
Explain why NO is key.
This naturally occurring molecule contains small signaling properties that play a critical role in IOP regulation via the activation of soluble guanylate cyclase (sGC; it regulates blood pressure and blood vessel relaxation).
- Nicox also reported that NO has a unique mechanism of action (MOA) that enhances aqueous humor drainage from the eye to provide additional IOP-lowering efficacy.
- Take note: This MOA differs from that of PGAs, which typically reduce IOP by increasing the uveoscleral outflow pathway.
And how does this benefit NCX 470?
The NO-donating, PAG bimatoprost combination contains a dual MOA that, according to the company, has been clinically proven to achieve superior IOP lowering.
How it works: The eye drop (NCX 470) is formulated to release bimatoprost and NO directly into the eye via two different target pathways—resulting in IOP reduction for both OHT and OAG patients.
Alrighty, now about the exploratory study.
First, take note: Although the Whistler exploratory trial was a phase 3b study, it will not be included (and is not required to be included) in any future new drug application (NDA) submission for NCX 470.
As such: The phase 3 clinical programs approved for inclusion in an NDA package—comprised of the Mont Blanc (NCT04445519) and ongoing Denali (NCT04630808) trials—have already demonstrated the safety and efficacy of the candidate.
- See here for the latest findings from the Mont Blanc trial (reported in March 2025), in which NCX 470 met the efficacy standard of IOP lowering for FDA approval.
So why conduct this trial?
Investigators wanted to evaluate NCX 470’s MOA on two aqueous humor parameters that have not been studied in the other phase 3 trials:
- Trabecular meshwork (TM)
- Outflow and episcleral venous pressure (EVP)
Gotcha. Next: Give me the rundown on its setup.
- The design: A double-masked, placebo-controlled trial (NCT05938699)
- The participants: 18 healthy patients (≥ aged 18) with OHT
- The setup: Participants received either one of the following in a randomized eye
- One drop of NCX 470 01%
- One drop of an artificial tear placebo
- The duration: ~8 days
- Note: Measurements were taken at baseline and after 8 days at 1 p.m., as well as (for some parameters) at 3 p.m.
- The outcome measure: Change from baseline in aqueous humor dynamics (AHD)
And the resulting data?
Nicox shared two key findings:
- Changes in the aqueous humor flow rate trended toward significance when compared to placebo (p = 0.072)
- Outflow facility was positive at 1 p.m. (p = 0.081) and significant at 3 p.m. (p = 0.001)—as was diurnal outflow
The reason for this change: Was reportedly due to the effect of NO on the TM.
Noted. What else?
The company reported IOP lowering and uveoscleral outflow to be “statistically significant at all timepoints measured” (including 1 p.m. and 3 p.m.).
Conversely: Episcleral venous pressure did not show any notable trends.
Any adverse events?
None were reported.
So what’s significant about these findings?
With this exploratory trial’s data, the candidate has demonstrated its potential as “an approvable and differentiated asset with a promising clinical profile,” according to Doug Hubatsch, Nicox’s chief scientific officer.
More specifically: The latest numbers support NCX 470’s IOP-lowering MOA via two different pathways:
- Conventional (NO-stimulated)
- Uveoscleral (prostaglandin-stimulated)
Nice! Looking ahead … how soon could we see an NDA submission?
As Nicox previously shared, the company is planning for a potential H2 2026 submission.
But in the meantime: Keep your eyes out for topline results from the Denali trial sometime in Q3 2025.