Research platform

Nitric oxide (NO)-donors: the Nicox expertise

Nicox has developed a world-leading position in the therapeutic application of NO-donating compounds, based on a strong research platform which creates New Molecular Entities (NMEs). Our specialized Research Center in Italy has worked on many R&D studies covering various therapy areas such as cardiovascular, inflammation and ophthalmology creating one of the most significant patent portfolios in the area. Nicox’s compounds, known as NO-donors, are designed to donate nitric oxide with a sustained pharmacological effect at tissue level aiming at avoiding the drawbacks related to the rapid burst of nitric oxide associated with traditional nitrates.

Focus on ocular disorders

In line with Nicox’s strategic positioning in the ophthalmic space, the research platform is now focused on ocular diseases where nitric oxide (NO) has been shown to play an important role. A specialized team in Nicox’s Italian research subsidiary, Nicox Srl, is pursuing targeted projects in collaboration with external research centers. This will enable Nicox to enhance its knowledge of the role and potential of nitric oxide (NO) in the eye and to leverage its long-standing expertise in the therapeutic application of NO-donating compounds. Many studies show that nitric oxide is involved in the eye’s physiology and pathophysiology. The phase 3 results for latanoprostene bunod confirmed the strong potential of our NO-donating proprietary research platform in ophtalmology.

Our Research team has developed additional NO-donating prostaglandins, including NCX 470, in the glaucoma area and, in collaboration with Universities and other Research Institutions, is currently focused on our next generation of stand alone NO-donors.

The role of NO in the ocular field

Nitric oxide (NO) is an endogenous cell-signaling molecule of fundamental importance in physiology and the subject of considerable scientific interest in recent years. NO and other molecules involved in NO-mediated signaling are present in ocular tissues. Studies have shown that topical or systemic administration of classic NO-donors (nitroglycerine, isosorbide dinitrate) in patients reduce intraocular pressure (IOP), supporting a role for NO in the regulation of IOP. This is of particular interest in the potential treatment of glaucoma, which is often associated with an increased IOP and can eventually lead to blindness if not treated.


Kotikoski et al. J Ocul Pharmacol Ther, 2002, 18:11-23; Schumann et al. Exp Eye Res,1994, 58:99-105; Nathanson et al. J Pharmacol Exp Ther, 1992, 260:956-65 ; Krauss et al Exp Eye Res, 2011, 93, 250-55; Cavet et al IOVS, 2014, 55, 5005-15

Disease focus areas
Glaucoma affects millions of patients worldwide and can lead to blindness if not treated.

What is glaucoma?

Glaucoma is a group of ocular diseases in which the optic nerve is injured, leading to the loss of the peripheral visual field. Glaucoma can eventually lead to blindness if not treated. Glaucoma is frequently linked to abnormally high pressure in the eye (intraocular pressure, IOP), due to blockage or malfunction of the eye’s drainage system. In 2010, Open Angle Glaucoma (the most common form of glaucoma) is estimated to affect 8 million individuals in the 7 worldwide major markets (US, Japan, UK, France, Germany, Italy, Spain).

Glaucoma symptoms and causes

Abnormally high IOP does not cause any symptoms itself, however it can lead to optic nerve damage and vision loss if left untreated. In the healthy eye, a small amount of aqueous humor (the liquid present inside the eye ball) is continually produced, circulates and flows out of the eye to maintain a constant eye pressure.

In glaucoma, the aqueous humor does not flow out of the eye properly, leading to a fluid pressure build up in the eye that will, over time, cause damage to the optic nerve fibers. The main risk factors for developing eye glaucoma are age, race and family history of glaucoma.

Glaucoma treatment options

Current medications are targeted at reducing high IOP to slow the progression of the disease. Numerous eye drops are available to either decrease the amount of fluid in the eye or improve its flow out of the eye. Unfortunately, most of the glaucoma patients do not take their medication properly due to the lack of symptoms. Several large trials have demonstrated that reducing IOP can prevent the progression of glaucoma in both early and late stages of the disease. A significant proportion of patients with elevated IOP require more than one medication to maintain their IOP within target levels, highlighting the need for more effective treatments.


The Ophthalmic Pharmaceutical Market Outlook to 2016 – Business insight, sept 2011, BI00042-019

Conjunctivitis is a very common eye disease with various causes.

What is conjunctivitis?

Conjunctivitis, also called red eye, is an inflammation of the conjunctiva (the thin layer of tissue that covers the white surface of the eye and the inner surface of the eyelids).  It is a common eye disease especially in children and may affect one or both eyes. More than 75 million people are estimated to suffer from allergic conjunctivitis in the United States1 and the prevalence of this disease ranges from 20% to 40%2-3.

Conjunctivitis symptoms and causes

Symptoms may include eye redness, excessive watering, itchy burning eyes, discharge, blurred vision and increased sensitivity to light. Conjunctivitis can be caused by a viral or bacterial infection, or can be the result of an allergic reaction (45%, 45% and 10% of the cases, respectively).

Viral conjunctivitis

As many as 90% of the viral conjunctivitis cases may be caused by adenovirus. Adenoviral conjunctivitis is highly contagious (up to 50% transmission rate) and, unlike bacterial conjunctivitis, which is usually self-limiting, it is associated with significant morbidity (decreased visual acuity or light sensitivity from persistent subepithelial infiltrates, chronic dry eye, visual loss from conjunctival foreshortening and scarring). There are currently no approved treatments for adenoviral conjunctivitis.


Allergic conjunctivitis

For certain patients, the presence of allergens (substances that can trigger an allergic reaction) in the eye leads to allergic conjunctivitis. This may be seen seasonally, for example with certain types of pollens in the summer, or may be present year round, with allergens including smoke, animal fur and pollution. When pharmaceutical treatment is required, patients usually take oral antihistamines, or eye drops containing antihistamines, mast cell stabilisers or corticosteroids.


O’Brien TP, Jeng BH, McDonald M, et al. Acute conjunctivitis: truth and misconceptions. Curr Med Res Opin. 2009 Aug; 25:1953-61.

  1. Global Data : Allergic Conjunctivitis Market Analysis, September 2014.
  2. Nathan RA, Meltzer EO, et al. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol 1997; 992:S808-S814.
  3. Singh K, et al. Epidemiology of ocular and nasal allergy in the United States, 1988-1994. Journal of Allergy and Clinical.
Blepharitis is a condition where the edges of the eyelids become red and swollen.

Blepharitis occurs in two forms:

  • Anterior blepharitis affects the outside front of the eyelids, where the eyelashes are attached, and is most commonly caused by bacteria (Staphylococcus epidermidis, Propionibacterium acnes, Corynebacteria spp. and Staphylococcus aureus), mites (such as Demodex folliculorum), and skin desquamation (seborrhea). 1
  • Posterior blepharitis affects the inner eyelids, the most part which makes contact with the eye, and is most commonly caused by problems with the oil (Meibomian) glands. Acne rosacea and scalp dandruff can also cause posterior blepharitis.

Because blepharitis often coexists with other related conditions, such as dry eye, it is difficult to study, and there is little consensus on the prevalence of the disease. Studies do show, however, that blepharitis is one of the most common conditions encountered in clinical practice 1. Of patients seen by ophthalmologists and optometrists, 37% and 47%, respectively, present with signs of the disease.


There is currently no FDA-approved drug product for the treatment of blepharitis, which limits Nicox’s ability to estimate prevalence and market size. Current standard of care includes lid hygiene products, anti-inflammatories, antibiotics, and combinations of anti-inflammatory and antibiotic agents1. Surveys reveal that ophthalmologists consider anti-inflammatory activity to be the most important product attribute when selecting a treatment for both forms of blepharitis, which supports the development of NCX 4251, an anti-inflammatory agent 2.


  1. Jackson WB. Blepharitis: current strategies for diagnosis and management. Can J Ophthalmol. 2008;43:170-9.
  2. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf. 2009; (2 Suppl):S1-S14.
Anterior ocular inflammation and irritation