About RetiNova Therapeutics
The First Regenerative Therapy For Retinal Ischemic Diseases
RetiNova Therapeutics is developing the first of a new class of regenerative therapies designed to reverse vision loss associated with retinal ischemia (lack of blood flow). Our Noregen™ program, currently in late preclinical development, will advance the standard of care for diabetic macular edema (DME) and retinal vein occlusion (RVO), going beyond the symptomatic control achieved by the current generation of drugs to achieve disease modification and regeneration of functional retinal tissue. This promises to revolutionize treatment outcomes for millions of patients worldwide with vision-threatening progressive disease.
A New Approach To Treatment Of Vision Loss
Vision loss due to ischemic retinal damage is an urgent, global, unmet medical need, driven by aging populations and a rising tide of chronic illnesses like cardiovascular disease, diabetes and obesity. Current standard-of-care treatments for retinal ischemic diseases such as diabetic macular edema (DME) and retinal vein occlusion (RVO) are aimed at blockading elevated levels of vascular endothelial growth factor (VEGF). VEGF over-production results from retinal oxygen deprivation, causing capillary hyperpermeability and in more severe cases also stimulating pathologic new blood vessel formation. Without the accompaniment of the master regulatory protein norrin, these new capillaries lack the tight endothelial cell junctions characteristic of a functional blood-retina barrier. Suppressing VEGF signaling with drugs like ranibizumab and aflibercept can prevent leakage from pre-existing capillaries and cause pathologic new vessels to regress. This can improve visual acuity to a partial degree, but the effects are time limited and require frequent re-injections. Since anti-VEGF drugs silence the pro-angiogenic signal they fail to address the underlying ischemia – at best they can only slow disease progression while patients are receiving them. Retinal function loss consequent to neuronal cell death is permanent. New therapies are urgently needed that repair retinal capillary cellular junctions and transmembrane leakage, regenerate new neuronal and capillary cells, and protect against further damage and loss of these capillary and neuronal cells.
Noregen™ Is The First Complete Norrin Mimic
Preserves The Full Spectrum Of Norrin's Retinal Regenerative Actions
Noregen™ (CTR-107) is a synthetic protein modeled after the naturally occurring protein norrin, an atypical Wnt signaling pathway ligand expressed only in tissues where specialized capillaries form a barrier between the circulation and delicate neural cells. Research by RetiNova’s founding scientists and clinicians has contributed to the discovery that norrin plays a crucial role in orchestrating formation of the retinal neurovascular unit during embryological development, with the correct patterning of vascular endothelial cells to promote and sustain a healthy blood-retina barrier. Crucially, our preclinical development work has shown that Noregen can switch this developmental program back on in the adult eye after ischemic damage to the retina, stimulating regeneration of specialized retinal vasculature, restoration of the vital blood-retina barrier and proliferation of neuronal and ganglion cell types responsible for conducting light to the optic nerve. Together, these activities are anticipated to contribute to restoration of vision, which we plan to explore in clinical trials.
In preclinical disease models we have shown that Noregen™ can:
- Rescue capillary growth, regrowing retinal vessels with a single intravitreal injection;
- Counteract VEGF-induced retinal edema : Noregen™ treated eyes have reduced leakage and improved vascularization following VEGF insult;
- Activate progenitor stem cells and stimulate both vascular and neuronal growth in concert;
- Promote glial cell growth that is needed for angiogenesis and neurogenesis;
- Prevent harmful fibrosis in retinal tissue via antagonism of pro-fibrotic growth factors TGF-ß and BMP2/4.
Because Noregen™ is the first and only complete norrin mimic that preserves all the beneficial activities of natural norrin, we believe that it is the only program in development with the potential to regenerate lost retinal function and achieve unrealized vision gains through targeted anti-permeability, anti-ischemic, anti-fibrotic, and neuro-protective effects.
Targeting Major Unmet Clinical Need
Diabetic Macular Edema (DME)
In diabetic patients, chronic hyperglycemia frequently results in retinal microvascular damage and ischemia which in turn causes VEGF upregulation. Downstream consequences of this VEGF over-expression include breakdown of the blood-retinal barrier, vascular hyperpermeability and visual disturbance from fluid accumulation in the macula. The International Diabetes Federation estimates that by 2045, 45 million people worldwide will suffer from visually threatening diabetic retinopathy, of which 29 million will have clinically significant DME. In 2023, approximately 500,000 patients in the United States received treatment with anti-VEGF drugs for this indication, at a direct cost of $3.4 billion. And yet, only one third of these patients achieved the goal of three-line improvement in visual acuity and two thirds had continuing symptoms of macular edema.
Retinal Vein Occlusion (RVO)
Retinal vein occlusions are blockages in the vessels draining the retinal circulation. There are two types: central retinal vein occlusions (CRVO) and branch retinal vein occlusions (BRVO) depending on involvement of larger or smaller vessels in the retina. Many cases result from hardening of the arteries (atherosclerosis), which run adjacent to the veins and compress them akin to stepping on a garden hose. This blocks blood drainage from the retina and can cause vascular dilation, ischemia, hemorrhage and fluid leakage (macular edema) in the retina, which can be visually debilitating. Patients may have risk factors including uncontrolled high blood pressure, obesity, heart disease, or glaucoma, and some younger patients may have blood clotting disorders. In the United States, around 300,000 people annually receive anti-VEGF treatments for RVO, driving direct drug sales of c. $1.3 billion. Similar to the situation with DME, only around one third of these patients achieve optimal improvements in visual acuity, indicative of an urgent need for a new generation of regenerative therapy.
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RetiNova Therapeutics Inc.
9191 Towne Center Drive, Suite 125, San Diego, CA 94402, USA
