trabodenoson (INO-8875) / Rocket Pharma - LARVOL DELTA

Adenosine: The common target between cancer immunotherapy and glaucoma in the eye. (PubMed, Life Sci) - "However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma."

Journal • Review • Glaucoma • Immune Modulation • Immunology • Inflammation • Ocular Inflammation • Oncology • Ophthalmology

ATP and Adenosine in the Retina and Retinal Diseases. (PubMed, Front Pharmacol) - "This mini-review focuses on the roles of ATP and adenosine in three types of blinding diseases including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Several agonists and antagonists of ATP receptors and adenosine receptors (ARs) have been developed for the potential treatment of glaucoma, DR and AMD: antagonists of P2X7 receptor (P2X7R) (BBG, MRS2540) prevent ATP-induced neuronal apoptosis in glaucoma, DR, and AMD; A1 receptor (A1R) agonists (INO-8875) lower intraocular pressure in glaucoma; A2A receptor (A2AR) agonists (CGS21680) or antagonists (SCH58261, ZM241385) reduce neuroinflammation in glaucoma, DR, and AMD; A3 receptor (A3R) agonists (2-Cl-lB-MECA, MRS3558) protect retinal ganglion cells (RGCs) from apoptosis in glaucoma."

Journal • Review • Age-related Macular Degeneration • Complement-mediated Rare Disorders • Diabetic Retinopathy • Glaucoma • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders

Trabodenoson and trabecular meshwork rejuvenation: A comprehensive review of clinical data. (PubMed, Expert Opin Investig Drugs) - "Its Phase 3 pivotal clinical trials failed at the wrong dose and dosing regimen because of the misinterpretation of the complex IOP results from the Phase 2 monotherapy and combination studies. The future development should focus on the TM benefits whilst unleashing its potential of neural protection through nanoparticle eye drops, medical coating and sustained release drug delivery."

Clinical data • Journal • Review • Glaucoma • Hypertension • Ophthalmology • MMP2

Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs. (PubMed, FEBS Lett) - "In order to assist structure-based discovery efforts for repurposing drugs against this disease, we constructed knowledge-based models of SARS-CoV-2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID-19."

Journal • Novel Coronavirus Disease

Adenosine receptor targeting in health and disease (Expert Opin Investig Drugs) - Selective ligands of A1, A2A, A2B & A3 adenosine receptors are likely to find applications in the treatment of pain, ischemic conditions, glaucoma, asthma, arthritis, cancer & other disorders in which inflammation is a feature; The aim of this review is to provide an overview of the present knowledge regarding the role of these adenosine receptors in health & disease

Expert opinion • Cardiovascular

Trabodenoson, an Adenosine Mimetic With A1 Receptor Selectivity Lowers Intraocular Pressure by Increasing Conventional Outflow Facility in Mice. (PubMed, Invest Ophthalmol Vis Sci) - "Parallel experiments in 3D-HTM showed that trabodenoson treatment significantly increased MMP-2 activity and MMP-14 abundance, while decreasing fibronectin and collagen IV expression. Trabodenoson alters ECM turnover by TM cells and increases conventional outflow facility, which accounts for its ability to lower IOP in young and aged mice."

Journal • Preclinical • Biosimilar

Study of Fixed-Dose Combinations of Trabodenoson and Latanoprost in Adults With Ocular Hypertension or Primary Open-Angle Glaucoma (clinicaltrials.gov) - P2; N=165; Not yet recruiting; Sponsor: Inotek Pharmaceuticals Corporation

New P2 trial • Biosimilar • Cardiovascular • Glaucoma • Ophthalmology

Topical Trabodenoson Is Neuroprotective in a Rodent Model of Anterior Ischemic Optic Neuropathy (rNAION). (PubMed, Transl Vis Sci Technol) - "Selective adenosine A agonists may prove an appropriate neuroprotective adjunctive for ischemia-related ON diseases such as NAION and glaucoma. RGC and ON neuroprotection in ischemic neuropathies may be achievable by topical administration of A adenosine agonists rather than by simply relying on intraocular pressure reduction."

Journal • Preclinical

Analysis of Trabodenoson’s neuroprotective effect in a rodent model of NAION (ARVO 2019) - "It increased ONH expression of genes associated with astrocyte-related neuroprotective mechanisms. This suggests that Trabodenoson exert direct neuro-protective effects distinct from its antihypertensive effects, targeted to the ONH, may be an appropriate adjunctive therapeutic for optic nerve diseases such as NAION and open angle glaucoma."

Preclinical