In the Cards

Jan 16, 2024

The two most advanced indications for RRx-001 (nibrozetone) are in oncology as a chemosensitizer for the treatment of small cell lung cancer (SCLC) (Phase 3 REPLATINUM) and as a chemoradioprotector for the mitigation of severe oral mucositis (SOM) (Phase 2b KEVLARx). The FDA awarded RRx-001 (nibrozetone) Fast Track status based on its anti-SOM activity in the Phase 2a PREVLAR clinical trial. Indications that are also under investigation for RRx-001 include endometriosis, and the neurodegenerative diseases, Parkinson’s and ALS/MND, based on grants awarded by the Michael J. Fox Foundation and FightMND, respectively.

Notwithstanding how well RRx-001 (nibrozetone) has performed—and continues to perform— in these different disciplines, we strongly suspect that the one most ideally suited for its unique mechanisms of action is cardiology or “cards,” for short.

This is because in addition to its well documented anti-inflammatory and antioxidative properties, RRx-001 (nibrozetone) is a potent nitric oxide (NO) donor but only—and here’s the interesting part—under poorly oxygenated or hypoxic conditions. One of the main functions of nitric oxide is as a vasodilator that opens or dilates blood vessels.

Of the FDA approved NO donors, including nitroglycerin (GTN), isosorbide dinitrate (ISDN), isosorbide mononitrate (IS-5N), amyl nitrite, and sodium nitroprusside (SNP), all release nitric oxide systemically, which is responsible for several side effects including headaches, low blood pressure or hypotension, methemoglobinemia and rapid heart rates or tachycardia. By contrast, because RRx-001 (nibrozetone) is the only nitric oxide donor to release NO locally in situ under hypoxic conditions and not systemically, these side effects are not associated with it.

In several preclinical experiments, RRx-001 (nibrozetone) has demonstrated excellent activity in several cardiovascular disease (CVD) indications including pulmonary hypertension, myocardial infarction, stroke, diabetes, atherosclerosis and hyperlipidemia, ischemia-reperfusion injury, hemorrhagic shock and protection against doxorubicin-induced cardiomyopathy.

RRx-001 (nibrozetone) is destined to be used in the clinic as a treatment for coronary heart disease.

One might also say that it’s in the cards.