By EpicentRx Staff
When Paul Ehrlich, regarded as the founding father of the modern pharmaceutical industry, coined the term “magic bullet” (“Zauberkugel,” in German) in 1908, he set something in motion. The term is used to signify drugs or therapies that target distinct diseases with super specificity, and ever since, research and development efforts have gradually shifted to the one-drug-one-target strategy, which predominates today. It’s based on rational or precision design, rather than chance observation and serendipity.
With the more recent arrival of NLRP3 and gasdermin D (GSDMD) inhibitors, compounds which inhibit the inflammatory response, Ehrlich’s “magic bullet” term has taken on an expanded meaning. It includes therapies that specifically target many diseases rather than one –the common denominator and root cause of which is inflammation. “NLRP3 and pyroptosis blockers for treating inflammatory diseases,” published in the prestigious journal, Trends in Pharmacological Sciences (TIPS), prominently features EpicentRx’s lead small molecule, RRx-001.
The “magic bullet”-like properties of RRx-001 interact with several therapeutic targets, including NLRP3, to treat a range of indications such as cancer, acute radiation syndrome, NASH, sickle cell disease, sepsis, Parkinson’s and Alzheimer’s Diseases, inflammatory bowel, and cardiopulmonary disorders. An underlying event and major driver of many of these conditions is hyperactivity of the NLRP3 inflammasome and its downstream regulators like gasdermin-D (GSDMD), the several inhibitors of which, highlighted in the review, are on the critical path to approval.
Different from these other inhibitors, RRx-001 has been administered to more than 300 patients in 12 clinical trials in the absence of any severe RRx-001 related side effects. The safety profile of RRx-001 permits unique combinations of RRx-001 with other pharmaceutical agents that impact the inflammasome. Also different from the other inhibitors in the review, RRx-001 is in a Phase 3 clinical trial for the treatment of small cell lung cancer (SCLC) and a soon-to-start trial in first line head and neck cancer for protection against the radiation- and chemotherapy-driven development of severe oral mucositis (blistering in the mouth). In addition, the different mechanisms of action of RRx-001, which include NLRP3 inhibition, Nrf2 activation, CD47 downregulation, and nitric oxide donation only under low oxygen or hypoxic conditions, further differentiate RRx-001 from these other inhibitors and make RRx-001 potentially better suited for the treatment of complicated diseases, such as Parkinson’s or cancer, where multiple pathways and targets are involved.
The inflammasome review by Rebecca Coll, Kate Schroder, and Pablo Pelegrin concludes, “…inflammasome blockers show enormous promise as a new generation of anti-inflammatory drugs for a wide range of conditions currently lacking curative treatments.” This perfectly summarizes the potential “magic bullet” therapeutic role of RRx-001, as an inflammasome blocker that may treat and prevent several unmet medical needs.