The Lead Compound ─ Lipophilic, Anti-angiogenic & More
NeuMedics compounds are proprietary and protected under US patent 8338477 issued December 25th, 2012.
NeuMedics lead compound, NM108 is a small molecule proprietary analog that has been confirmed to be room temperature stable, lipophilic, and "non-antibiotic" – while retaining the potent anti-inflammatory, anti-oxidant, and anti-apoptotic properties common to this class of drugs with similar scaffolds. Together these properties make NM108 nearly ideal for the treatment of Diabetic Macular Edema (DME) as well as other inflammatory diseases, as has been shown in multiple studies and animal models. Because of their well-documented and significant systemic side effects—including the potential for the development of antibiotic resistance—currently available systemic tetracyclines have not been and are unlikely ever to be approved for chronic use for non -infectious indications, especially for patients who are immunocompromised and have other significant comorbidities.
NM108 is highly lipophilic: The active ingredient of NM108 is highly lipophilic, resulting in wide distribution and tissue concentrations that often exceed those of plasma. Initial studies of the parent molecule administered topically to rabbit eyes in a rabbit healthy preclinical model show achievement of effective concentrations in important retinal tissues.
NM108 is anti-angiogenic: NM108 is known to have important anti-angiogenic effects, including inhibition of collagenase and matrix metalloproteinase (MMP), both of which are important for new vessel growth. The MMP's are a family of proteinases that also cleave structural components of the extracellular matrix (ECM) as well as other proteins, including growth factors. MMP's can release ECM-bound VEGF-A. Their activation can contribute to the breakdown of the Blood Retinal Barrier (BRB) by degrading ECM proteins as well as releasing growth factors.
Clinical studies show proof-of-concept
In a proof-of-concept study of DME funded by the National Eye Institute Intramural Research Program, oral minocycline, as the primary treatment, was associated with improved visual function, decreased central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. This study confirms that the anti-inflammatory effects of tetracycline analogs, such as minocycline and NM108, likely resulting from inhibition of intravitreal microglia, results in improved symptomatic visual outcomes in patients with DME. (ClinicalTrials.gov number, NCT01120899.)
Preclinical studies show proof-of-concept
Three separate preclinical studies have shown the beneficial effects of minocycline in terms of decreasing the permeability of RBR and reducing diabetes-related cytokine production in animal models of diabetic retinopathy