Pipeline, Markets and Science


Nicox products and product candidates

Pre-clinical Phase 1 Phase 2 Phase 3 NDA Marketed
Product candidates
NCX 470 | novel NO-donating prostaglandin analog
NCX 470 | novel NO-donating prostaglandin analog Glaucoma & Ocular Hypertension Partnered with Ocumension in the Chinese & SE Asian markets
Mont Blanc and Denali trials
NCX 4251 | fluticasone propionate nanocrystal suspension
NCX 4251 | fluticasone propionate nanocrystal suspension Dry Eye Disease Partnered with Ocumension in the Chinese & SE Asian markets
NCX 1728 | NO-donating PDE5 inhibitor
NCX 1728 | NO-donating PDE5 inhibitor Glaucoma & Ocular Hypertension and Retinal Diseases
Out-licensed commercial products
VYZULTA®
VYZULTA®
Licenced to Bausch + Lomb: worldwide
ZERVIATE®
ZERVIATE®
Licenced to Eyevance: United States
Licenced to Ocumension Therapeutics: Chinese & Southeast Asian markets

Ophthalmology market

Glaucoma, Allergic Conjunctivitis and Dry Eye Disease
$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).
$3.8bn

Dry eye disease market

The U.S prescription market for dry eye products in 2021 was estimated to be 8.4 million prescriptions for a value of $3.8 billion out of a $5 billion estimated worldwide market for dry eye disease treatment (data from Bloomberg).

Our portfolio at a glance

Product candidates


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 trial in November 2022
  • Top-line results from Denali after 2023

NCX 470 is a novel, potential best-in-class, nitric oxide (NO)-donating prostaglandin analog eye drop, 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 AbbVie, Inc., is one of the leading branded products in the class of prostaglandin analogs (PGAs). Prostaglandin analogs are the most widely used class of drugs for IOP-lowering in patients with open-angle glaucoma or ocular hypertension. Nitric oxide brings additional IOP-lowering efficacy by enhancing aqueous humor drainage from the eye via a different mechanism of action than that engaged by prostaglandin analogs. 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 worldwide until 2029 under a composition of matter patent with potential extension up to 5 years in the U.S. and EU and a formulation patent until 2039 in the U.S., EU, Japan and China.


NCX 1728

Lead compound in a new class of molecules based NO-mediated activity
NCX 1728 is an NO-donating PDE5 inhibitor under evaluation for development in glaucoma & IOP lowering and in certain retinal diseases

NCX 1728, an NO-donating PDE5 inhibitor, is the lead compound of a new class of compounds (non-PGA related) with NO-mediated IOP-lowering effects that are enhanced and prolonged by concomitant phosphodiesterase-5 (PDE5) inhibition activity within the same molecule. PDE5 inhibition has been shown to enhance the efficacy and the duration of NO-mediated effects. This class of molecules is being evaluated for development in glaucoma & IOP lowering and in certain retinal diseases. Optimization of ophthalmic formulations of NCX 1728 are underway prior to initiating nonclinical testing required for the filing of an IND application. In non-human primates, NCX 1741, an analog of Nicox’s development candidate NCX 1728, demonstrated reduction of IOP to a similar extent to that of travoprost, with faster onset of activity. Travoprost is a PGA, a class of molecules which are considered standard of care for IOP lowering in humans.


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 stage for dry eye disease

Expected milestones:

  • CMC preparation for next clinical trial

NCX 4251 is a novel patented ophthalmic suspension of fluticasone propionate nanocrystals, in development as a topical treatment, applied to the eyelid margins, for patients with dry eye disease. Fluticasone propionate has an affinity for the glucocorticoid receptor approximately ten times greater than dexamethasone, a corticosteroid commonly used in ophthalmology. NCX 4251 is being developed for application to the eyelid margins via an applicator, minimizing the potential steroid exposure through the cornea which can lead to damaging side effects such as intraocular pressure (IOP) increase found with current topical steroids.

Once-daily NCX 4251, fluticasone propionate ophthalmic suspension 0.1% was evaluated in the Mississippi Phase 2b clinical trial, versus placebo in patients with acute exacerbations of blepharitis. Following the encouraging post hoc results from the Mississippi Phase 2b clinical trial and a subsequent meeting with the U.S. Food and Drug Administration (FDA), the future development of NCX 4251 is focused on dry eye disease. The Mississippi post hoc results suggest that NCX 4251 is effective in reducing dry eye symptoms in patients who scored more highly for a key sign of dry eye disease (fluorescein staining). Statistically significant improvements in a number of dry eye symptoms and improvements in one sign (p=0.0524) were seen. 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. The future development of NCX 4251 in the U.S. will require initial manufacturing scale-up followed by two additional efficacy clinical trials, both evaluating one sign and one symptom of dry eye disease, long term safety data, and certain additional clinical and non-clinical data to support an NDA submission in the U.S. The remaining pharmaceutical, non-clinical and clinical development of NCX 4251 is not yet financed and therefore the Company has not planned yet the start of this last phase of development.

The primary outcome measure in the Mississippi trial 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.

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 patents until 2033 and to 2040 by additional patents granted in the EU and Japan).

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). VYZULTA is indicated for the reduction of IOP in patients with open-angle glaucoma or ocular hypertension in the U.S. At approval, VYZULTA was the first eye drop approved in the past 20 years with a novel approach to reduce IOP.

VYZULTA is commercialized in the U.S., Canada, Argentina, Hong Kong, Mexico, Taiwan and Ukraine by exclusive licensee Bausch + Lomb and approved in Brazil, Colombia, Jordan, Qatar, Singapore, South Korea, Turkey and United Arab Emirates. VYZULTA is covered by a composition of matter patent in the U.S. to 2024/2025, 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.  Positive results in February 2022 from a Phase 3 clinical trial in China, run by local partner Ocumension Therapeutics, required for a submission of a New Drug Application (NDA) for approval to commercialize ZERVIATE 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.

The ZERVIATE formulation is protected by granted patents in the U.S. to 2032, and in Europe, Japan and Canada to 2030.

For further details on ZERVIATE in the U.S., 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