Pipeline, Markets and Science


Nicox products and product candidates

Pre-clinical Phase 1 Phase 2 Phase 3 NDA Marketed
NO-donating product candidates targeting glaucoma
PC P1 P2 P3 NDA MKT
NCX 470 | novel NO-donating prostaglandin analog
NCX 470 | novel NO-donating prostaglandin analog
Mont Blanc and Denali trials
NCX 1728 | novel NO-mediated IOP lowering agent
NCX 1728 | novel NO-mediated IOP lowering agent
Pre-clinical Phase 1 Phase 2 Phase 3 NDA Marketed
Novel treatment to address unmet medical need in blepharitis
PC P1 P2 P3 NDA MKT
NCX 4251 | fluticasone propionate nanocrystal suspension
NCX 4251 | fluticasone propionate nanocrystal suspension
Out-licensed commercial products
VYZULTA®
VYZULTA®
Licenced to Bausch + Lomb: worldwide
ZERVIATE®
ZERVIATE®
Licenced to Eyevance: United States
Licenced to Ocumension Therapeutics: Chinese & South East Asian markets

Ophthalmology market

Glaucoma and Allergic Conjunctivitis
$6.0bn

Worldwide sales

Worldwide sales of treatments targeting glaucoma were over $6.0 billion, out of a $24.3 billion worldwide market for ophthalmic drugs in 2020. (data from IQVIA Analytics Link 2020).
$3.0bn

Glaucoma treatments

In the U.S., sales of treatments targeting glaucoma totaled $3.0 billion in 2020 or 27% of the $11.1 billion U.S. market for ophthalmic drugs (data from IQVIA Analytics Link 2020).
$360m

Allergic conjunctivitis market

The annual U.S. market for prescription treatment of allergic conjunctivitis totals approximately $360 million (data from IQVIA Analytics Link 2020).

Our portfolio at a glance

NO-donating products and product candidates targeting glaucoma


NCX 470

Nicox’s lead clinical product candidate
NCX 470, is a novel nitric oxide (NO)-donating prostaglandin analog, currently in a Phase 3 clinical program for the lowering of intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension.

Expected milestones

  • Top-line results from Mont Blanc in Q1 2023
  • Top-line results from Denali by end 2023

NCX 470 is a novel nitric oxide (NO)-donating prostaglandin analog, designed to release bimatoprost and NO into the eye to lower intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. NO is a well-known small naturally-occurring signaling molecule that plays a key role in the regulation of IOP through activation of soluble guanylate cyclase (sGC). Bimatoprost, marketed under the brand name LUMIGAN by Allergan, Inc., is the leading product by sales in the class of PGAs, the most widely used class of drugs for the treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension. We believe a novel dual mechanism of action can achieve superior IOP-lowering compared to the parent compound alone. NCX 470 has the same mechanism-of-action as our first marketed product in the U.S.

NCX 470 is currently in two multi-regional Phase 3 clinical trials, Mont Blanc and Denali, evaluating the IOP lowering efficacy of once-daily dosed NCX 470 ophthalmic solution 0.1% compared to latanoprost ophthalmic solution 0.005% in patients with open-angle glaucoma or ocular hypertension. Latanoprost, first marketed as Xalatan, is the most prescribed PGA in the U.S.

In the 28-day Phase 2 trial, Dolomites, NCX 470 demonstrated statistical superiority to latanoprost ophthalmic solution, 0.005%. NCX 470 0.065% was up to 1.4 mmHg superior in reducing IOP compared to latanoprost 0.005%, and 27% of patients on NCX 470 0.065% showed ≥ 3mmHg IOP lowering vs latanoprost 0.005%. NCX 470 0.065% achieved a reduction in IOP from baseline of 7.6 to 9.8 mmHg. We believe this is the highest IOP reduction from baseline ever reported in an eye drop glaucoma clinical trial. NCX 470 was well tolerated with no drug-related serious adverse events. The most common adverse event was conjunctival hyperemia.

NCX 470 is covered by U.S. patents to 2029 with potential for up to 5 year extension. Nicox received approval of a formulation patent for NCX 470 extending the patent coverage in the U.S., Europe and Japan to 2039.


NCX 1728

The first compound of a new class of NO-mediated intraocular pressure (IOP) lowering agents
NCX 1728 is currently in formulation optimization studies prior to initiating nonclinical testing required for the filing of an IND application.

NCX 1728 is the first in a new class of compounds with NO-mediated IOP lowering effects that are enhanced and prolonged by concomitant phosphodiesterase-5 (PDE5) inhibition within the same parent molecule. PDE5 inhibition has been shown to enhance the efficacy and the duration of NO-mediated effects. Molecules in this class demonstrated IOP lowering efficacy similar to travoprost in animal models of ocular hypertension and glaucoma. This class of compounds have potential for use as monotherapy, as adjunctive therapy or in fixed-dose combinations with prostaglandin analogs (PGAs) for lowering IOP in patients with open-angle glaucoma or ocular hypertension.

Novel treatment to address unmet medical need in blepharitis


NCX 4251

A novel, patented, ophthalmic suspension of fluticasone propionate nanocrystals
NCX 4251, a novel, patented, ophthalmic suspension of fluticasone propionate nanocrystals, is in clinical development for acute exacerbations of blepharitis.

Expected milestones:

  • Next steps to be discussed with the U.S. Food and Drug Administration in a meeting in early 2022

NCX 4251 is a novel, patented, ophthalmic suspension of fluticasone propionate nanocrystals, in development as a topical treatment of the eyelids for patients with acute exacerbations of blepharitis. Fluticasone propionate has an affinity for the glucocorticoid receptor which is approximately ten times greater than dexamethasone, a corticosteroid commonly used in ophthalmology. NCX 4251 is being developed for direct administration to the eyelids via a unique applicator at the eyelids, applied directly to the site where the disease originates. This method of delivery minimizes the intraocular exposure to the steroid fluticasone, thereby reducing the risk of developing increased intraocular pressure (IOP) and cataract. There are currently no FDA approved treatments for acute exacerbations of blepharitis in the U.S.

The Mississippi Phase 2b clinical trial evaluated once-daily dosed NCX 4251, fluticasone propionate ophthalmic suspension 0.1%, versus placebo in patients with acute exacerbations of blepharitis. The primary outcome measure was the proportion of patients achieving complete cure in all three hallmark signs and symptoms of blepharitis, eyelid redness, eyelid debris and eyelid discomfort, at Day 15, with two secondary outcome measures on signs and symptoms of dry eye. The trial did not meet the primary or secondary efficacy endpoints. However, a signal of NCX 4251’s potential efficacy was seen in the trial with NCX 4251 0.1% showing a numerical improvement over placebo in the primary outcome measure of complete cure in eyelid redness, eyelid debris and eyelid discomfort at Day 15. NCX 4251 also showed a statistically significant difference against placebo in the exploratory endpoint of change from baseline in the composite score of the same key signs and symptoms at Day 8 (p=0.03), Day 11 (p=0.01) and Day 15 (p=0.01). Data analysis is continuing in order to decide on the key signs and symptoms of focus for future development.  NCX 4251 was found to be safe and well-tolerated over 14 days’ treatment, with no serious adverse events, and all of the adverse events for the NCX 4251 treatment arm were mild. There were no discontinuations in the study due to an adverse event.

In the Danube Phase 2 trial, NCX 4251 0.1% demonstrated statistically significant reductions in the signs and symptoms of blepharitis in the prospectively defined pooled analysis of once-daily (QD) and twice daily (BID) NCX 4251. The NCX 4251 0.1% QD treatment was selected to advance into a larger Phase 2 clinical trial. The selected dose NCX 4251 0.1% also demonstrated promising efficacy against exploratory endpoints in the trial in reducing the signs and symptoms of dry eye disease. Both once daily and twice daily NCX 4251 0.1% were well tolerated and there were no serious adverse events, no treatment related systemic adverse events and no adverse events of intraocular pressure elevation, the most common side effect of topical ophthalmic steroids.

Similar to ZERVIATE, we intend to seek regulatory approval for NCX 4251 using the FDA’s 505(b)(2) regulatory pathway. This enables us to rely, in part, on the FDA’s prior findings of safety and efficacy for fluticasone propionate, or published literature, in support of our NDA.

NCX 4251 is covered worldwide by granted patents to 2033, and to 2040 by an additional patent granted in the EU.

Out-licensed commercial products


VYZULTA®

A prostaglandin analog with one of its metabolites being nitric oxide (NO)
VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024%, indicated for the reduction of IOP in patients with open angle glaucoma or ocular hypertension. It is exclusively licensed worldwide to Bausch + Lomb, a wholly-owned subsidiary of Bausch Health Companies Inc. VYZULTA is commercialized in multiple countries including the United States, with other approvals and launches ongoing.

Expected milestones:

  • Ongoing global approvals and launches in newly approved geographies

VYZULTA, exclusively licensed worldwide to Bausch + Lomb, is a prostaglandin analog with one of its metabolites being nitric oxide (NO), indicated for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension. At approval, VYZULTA was the first eye drop approved in the past 20 years with a novel approach to reduce IOP.

Commercialized in the U.S., Canada, Argentina , Hong Kong, Mexico and Taiwan by exclusive licensee Bausch + Lomb and approved in Brazil, Colombia, Jordan, Qatar, Singapore, South Korea, Ukraine and United Arab Emirates for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension. VYZULTA is covered by a composition of matter patent in the U.S. to 2025, with eligibility for up to 5-year extension confirmed by the USPTO.

For further details on VYZULTA, please visit our partner’s dedicated website www.vyzulta.com.


ZERVIATE®

Indicated for the treatment of ocular itching associated with allergic conjunctivitis

ZERVIATE® (cetirizine ophthalmic solution), 0.24%, indicated for the treatment of ocular itching associated with allergic conjunctivitis, has been exclusively licensed in the U.S. to U.S. partner Eyevance Pharmaceuticals and is commercialized there since March 2020. ZERVIATE has been also exclusively licensed to Ocumension Therapeutics for development and commercialization in the Chinese and the majority of the South East Asian markets.

Expected milestones:

  • Ongoing global roll-out through partnerships

ZERVIATE is a novel, patented eye drop formulation of cetirizine approved in the U.S. for ocular itching associated with allergic conjunctivitis.

Commercialized in the U.S. by exclusive U.S. partner Eyevance Pharmaceuticals since March 2020 – Phase 3 clinical trial in China initiated by local partner Ocumension Therapeutics in December 2020 for a submission of a New Drug Application (NDA) in China.

Nicox has also signed exclusive license agreements with Samil Pharmaceutical for the development and commercialization of ZERVIATE in South Korea, with ITROM Pharmaceutical Group in certain Gulf and Arab markets and with Laboratorios Grin in Mexico.

Three U.S. patents cover ZERVIATE through 2032.

For further details on ZERVIATE, please visit our partner’s dedicated website https://myzerviate.com/.

Watch how our science works

Nitric oxide donation

The Nicox expertise

We have developed a leading scientific and strategic position in the therapeutic application of nitric oxide (NO)-donating compounds based on our internally-developed NO-donating research platform, specifically in ophthalmology, supported by an extensive patent portfolio.

This platform underpins our product candidates that target glaucoma, including VYZULTA®, our first approved product in the U.S., commercialized by our exclusive global licensee, Bausch + Lomb.


NO is a well-known small naturally-occurring signaling molecule whose target is an intracellular enzyme, soluble guanylate cyclase (sGC), which converts guanosine triphosphate to the second messenger, cyclic guanosine monophosphate (cGMP). The NO stimulated increase in the concentration of cGMP in the trabecular meshwork leads to the sequestration of intracellular calcium, the relaxation of the trabecular meshwork and, consequently, an increase in the outflow of the aqueous humor from the anterior segment of the eye through the primary or conventional outflow pathway. All of the foregoing events are thought to lead to lowering of intraocular pressure (IOP).

NO lowers IOP via distinct cellular and molecular pathways compared to other pharmaceutical agents currently used to treat ocular diseases including glaucoma and ocular hypertension. By designing our proprietary molecules with a dual mechanism of action, we may be able to achieve increased IOP lowering efficacy compared to the molecules acting by a single mode of action. Based on this approach, our partnered approved product VYZULTA®, the only NO donating molecule approved for an ophthalmic indication in the U.S., and our product candidate NCX 470 currently in clinical development, are comprised of a parent prostaglandin analog (PGA) and a NO-donating moiety.

We have also explored NO-donating compounds of different chemical and pharmacological classes in order to combine the NO donation effects with other existing MOA and thus to potentially increase the overall IOP lowering potentials of the resulting new molecular entities. Our lead research program is NO-donating PDE5 inhibitors (PDE5), fully owned by Nicox: PDE5 is a key enzyme that accelerates the degradation of the second messenger, cGMP produced by sGC following its stimulation by NO. By inhibiting PDE5 we may enhance and prolong the effect of NO on IOP reduction.


Publications