Following on from a previous post called, “A Blog About Smog,” is this one about Smaug, an antagonistic, treasure-hoarding dragon from J. R. R. Tolkien’s, The Hobbit. In “A Blog About Smog,” we describe the mechanism of action of lead EpicentRx therapy, RRx-001 (nibrozetone), as smog-like because it releases NOxious nitrogen oxides or NOx, key components of smog, but only in the vicinity of tumors.
Similarly, RRx-001 (nibrozetone) is Smaug-like because it keeps a watchful eye, so to speak, not over gold but platinum, as in platinum chemotherapy.
RRx-001 is not a dragon, of course, but it does belong to a Dragoon or armed unit consisting of platinum chemotherapy plus another agent or modality. Like Smaug, RRx-001 is antagonistic – but only to tumors where it spits nitric acid, not fire. Unlike Smaug, it potentially preserves and protects normal tissues through anti-inflammatory (inhibition of the NLRP3 inflammasome) and antioxidant (Nrf2 activation) mechanisms.
Currently, RRx-001 is administered with cisplatin/carboplatin plus etoposide in a Phase 3 clinical trial called REPLATINUM for the treatment of third-line or beyond small cell lung cancer (SCLC), a highly intractable tumor type. The hypothesis of REPLATINUM is that RRx-001 will sensitize or resensitize tumors, depending on their initial susceptibility, to platinum and etoposide from first line.
RRx-001 will also begin a Phase 2b clinical trial called KEVLARx with cisplatin and intensity-modulated radiation therapy (IMRT) in first line locally advanced head and neck cancer. The hypothesis of KEVLARx is that the addition of RRx-001 to cisplatin and radiation will prevent or mitigate the development of common, potentially dose-limiting toxicities like dysphagia or severe oral mucositis.
So, unlike Smaug, whose name is synonymous with desolation (see The Hobbit: The Desolation of Smaug), RRx-001 brings elation and exhilaration whenever it manages to shrink down tumors and/or protect normal tissues from toxicity.