The Disease

dm3Diabetic Macular Edema (DME)

DME is caused when fluid accumulates in the macula. It can develop without symptoms at any of the four stages of diabetic retinopathy (DR), though it typically occurs in the more advanced forms. It is found in almost 50% of people with proliferative retinopathy, the advanced stage of DR.

DME is a complex pathological process caused by multiple factors, including breakdown of the inner and outer blood-retinal barriers, oxidative stress, and elevated levels of vascular endothelial growth factor which have been demonstrated in both preclinical and clinical studies.

Treatment

Current effective interventions for DME include treatment of systemic risk factors, such as elevated blood glucose, blood pressure and dyslipidemia. Ophthalmic treatments include laser photocoagulation, surgery and intraocular pharmacotherapy. New drugs, which are given by intraocular injection, have emerged in recent years to become first line treatment for DME that affects the central macula with loss of vision.  Despite the use of molecular therapeutics targeting vascular endothelial growth factor (VEGF), the majority of patients do not recover good, functional vision, and show residual edema, necessitating repeated intravitreal injections. Early detection and treatment of DME can prevent vision loss that can be moderate to severe, and even permanent. Globally, 285 million people were estimated to be visually impaired in 2010, with 39 million completely blind. 21 million people were estimated in 2010 to live with DME worldwide.

Not only does vision loss drastically impede on the ability to live an independent high-quality life, its widespread prevalence also imposes a social and economic burden on individuals, communities and governments.

Direct injection into the eye remains an important limitation of many of these new treatments.  In addition the risks of endophthalmitis, retinal detachment, and other adverse events become cumulative over the years after repeated intra-vitreal injections.

Novel Compounds

NeuMedics compounds are patented  and tested to confirm:

Neumedics compounds are patented and tested to confirm:

NeuMedics central hypothesis is that increased inflammatory CC chemokine’s in the diabetic retina alter the blood-retinal barrier through the recruitment of immune cells. Despite the use of molecular therapeutics targeting vascular endothelial growth factor (VEGF), the majority of patients do not recover good, functional vision, and show residual edema, necessitating repeated intravitreal injections. The scientific gap is due to the present inability to completely block all the inflammatory mediators implicated in the pathogenesis of DME.

Evidence suggests that diabetic retinopathy is an inflammatory disease. The precise mechanism by which the chemokine’s and leukocytes initiate the inflammatory cascade and finally damages this barrier is not clear. CC chemokine’s (CCL2, 5 and 7) are significantly up regulated in the retinas of diabetic animals. Also, there is increased trafficking of monocytes into the retina along with activation of retinal microglia in diabetes. The NeuMedics  approach is innovative as it addresses a novel mechanism of stabilizing the initial step of leukocyte-endothelial interaction, the critical upstream bottleneck for diabetic macular edema.

Clinical Plan

clinplan2NM108

NeuMedics wrote and filed the patent for NM108 (#8,338477 issued December 2012 for NM108 and its chemical cohorts). NM108 is a naphthacene carboxamide derivative formulated into an eye drop based micro emulsion that is self administered. NM108 decreases inflammation by (i) inhibition of pro-inflammatory compounds through modulation of protein expression and RNA transcription, (ii) activation or depletion of specific phosphatases associated with inflammation, and (iii) decreasing vascular permeability – an upstream event in the inflammation cascade.  Importantly, studies conducted by the NIH (Cukras et al IOVS, June 2012 Vol. 53,No 7) have already demonstrated proof-of-concept for NM108, showing that the scaffold of the parent compound to NM108 is effective in both reducing inflammation and improving vision in patients with DME.  NM108, has been tested at independent laboratories to confirm that it retains the proven efficacy characteristics of the scaffold compound, but eliminates important safety issues associated with the scaffold. These compounds offer significant advantages over currently available therapies.

Clinical Development

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