Investigating the safety and efficacy of pillararene sulfates as novel and effective reversal agents for both steroidal and non-steroidal neuromuscular blocking agents.

Abstract Reversal Therapeutics, Inc. (Reversal), a Maryland-based pre-clinical company, is advancing the development of PILLAR[6]MAXQ (P6AS), a novel supramolecular sequestration platform designed to address the limitations of current neuromuscular blocking agent (NMBA) reversal agents. NMBAs are commonly used in surgical anesthesia, and while sugammadex (Bridion®) is the standard reversal agent, it is ineffective against non- steroidal NMBAs like cisatracurium. P6AS, a patent-pending reversal agent, has demonstrated potential to overcome this limitation by safely and effectively sequestering both steroidal (rocuronium, vecuronium) and non- steroidal NMBAs, offering a broader reversal spectrum. The project’s primary objective is to evaluate the safety and efficacy of P6AS and derivative analogues as reversal agents for both steroidal and non-steroidal NMBAs. Specifically, the project aims to: i) Develop and evaluate P6AS analogues to identify those with high affinity (100 nM) for both steroidal and non-steroidal NMBAs; ii) Test the biocompatibility of selected compounds in kidney and liver cells to assess their in vivo efficacy in reversing NMBA effects; and iii) Characterize P6AS and derived analogues’ pharmacokinetics, including absorption, distribution, metabolism, and excretion, in rodent and non- rodent species. The expected results of this project are to advance P6AS and potentially derivative analogues toward clinical application, addressing a critical gap by enabling fast acting reversal of non-steroidal NMBAs and potentially improving surgical outcomes.