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

The National Institute of General Medical Sciences (NIGMS) awarded $1,105,101 to Reversal Therapeutics Inc. on September 12, 2025, under the Biomedical Research and Research Training program (CFDA 93.859) to investigate the safety and efficacy of pillararene sulfates as reversal agents for neuromuscular blocking agents used in surgical anesthesia.

Reversal Therapeutics, a Maryland-based pre-clinical company, is developing Pillar[6]MAXQ (P6AS), a novel supramolecular sequestration platform intended to overcome limitations of current NMBA reversal agents. While sugammadex is the standard reversal agent, it is ineffective against non-steroidal NMBAs such as cisatracurium. P6AS is designed to safely and effectively sequester both steroidal NMBAs (rocuronium, vecuronium) and non-steroidal NMBAs, offering a broader reversal spectrum.

The project work includes developing and evaluating P6AS analogues to identify compounds with high affinity for both steroidal and non-steroidal NMBAs; testing biocompatibility of selected compounds in kidney and liver cells to assess in vivo efficacy in reversing NMBA effects; and characterizing pharmacokinetics, including absorption, distribution, metabolism, and excretion, in rodent and non-rodent species. The expected outcome is to advance P6AS toward clinical application, enabling fast-acting reversal of non-steroidal NMBAs and potentially improving surgical outcomes.

Performance occurs in Massachusetts. The period of performance runs through August 31, 2026. The award is structured as a Project Grant, an assistance type supporting investigator-initiated biomedical research.

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.