The intriguing premise of a new Apple TV sci-fi-thriller, Dark Matter, based on a best-selling novel of the same name is that myriad parallel universes or multiverses constantly arise from all possible choices, or decisions, which are made or not made. The show’s protagonist, Jason Dessen, a happily married high school physics professor and father of one, who gave up on his dream of a promising research career for domestic tranquility, comes face-to-face with the road not taken and the trade-offs he made when he is kidnapped by an alternate version of himself, Jason #2, a genius inventor without a family, and forced to swap places with him in an alternate reality.
This got us thinking — where would our lead small molecule, RRx-001 (nibrozetone), have ended up if we hadn’t made the decision early on to evaluate it in cancer? Impossible to know, of course, without the benefit of multiversal travel device, but we strongly suspect that RRx-001 (nibrozetone) — call it RRx-001 (nibrozetone) #2 in this case — would have been used to treat and manage patients with vascular, and cardiopulmonary diseases. This suspicion is based on accumulated preclinical and clinical data, which demonstrate that RRx-001 (nibrozetone) abundantly donates the vasodilator molecule, nitric oxide (NO), but only under conditions of low oxygen or hypoxia.
The significance of such targeted NO donation is as follows. All FDA approved nitric oxide donors such as nitroglycerin (GTN), isosorbide dinitrate (ISDN), isosorbide mononitrate (IS-5N), amyl nitrite, and sodium nitroprusside (SNP) and even to best knowledge all other nitric oxide donors currently in development release NO everywhere under oxygenated and deoxygenated conditions alike. This limits their potential benefit because the NO release and distribution is not specific to diseased cells or tissues vis-à-vis healthy/normal ones. The lack of specificity further predisposes to the development of major systemic side effects known to occur with nitric oxide donors like hypotension, syncope or loss of consciousness, and methemoglobinemia.
By contrast, RRx-001 (nibrozetone) tightly focuses its NO release on the tissue(s) or organ(s) where disease or injury is present, which decreases any potential for toxicity, and possibly makes it the ideal treatment for several cardiopulmonary diseases like heart failure, pulmonary hypertension, and heart attack, as preclinical experiments have convincingly demonstrated.
Another potential indication for RRx-001 (nibrozetone) — call this one RRx-001 (nibrozetone) #3 — is as an anti-infective, since the molecule has already demonstrated excellent activity in the clinic against severe COVID-19 which this case EpicentRx-authored report documents and in the lab against malaria, tuberculosis, and sepsis.
That said, we are in an enviable position now with RRx-001 in a Phase 3 clinical trial called REPLATINUM for the treatment of small cell lung cancer (SCLC), and in a Phase 2b clinical trial called KEVLARx for the prevention/mitigation of severe oral mucositis. So, as intriguing as these alternate possibilities and realities are — and they certainly are intriguing to us — we like happily married Jason #1 from Dark Matter have no need or desire to explore any grass-is-greener scenarios with other RRx-001 doppelgangers.