689: Latest Progress Of Preclinical And Clinical Studies On RFUS-949, A Novel Sigma-1 Receptor Antagonist

Topic: Experimental (Non-clinical) Human Studies
Subtopic: Pain Category (ICD-11), Acute postsurgical pain, Pharmacological treatments, Assessment and Measurement of Pain/Nociception, Drug development

Background and Aims: There is a critical need for new analgesics acting through new mechanisms with much less adverse events (AEs) to existing pain therapies. Sigma-1 receptor (S1R), a chaperone protein highly expressed in different pain areas of central nervous system and peripheral nervous system, interacts and modulates the pain functionality of different receptors and ion channels. Recently, S1R has become a focus point of new drug discovery for a therapeutic target as the potential non-opioid analgesics for inflammatory and neuropathic pain, as its antagonists effectively ameliorate pain in both preclinical and clinical studies.

Methods: To evaluate the safety and efficacy of RFUS -949, the preclinical studies of its in vitro and in vivo pharmacology, pharmacokinetics and safety for IND application have been carried out. Currently the Phase I studies in the healthy volunteers on RFUS-949 are ongoing.

Results: RFUS-949 demonstrated a high and selective binding affinity for S1R. We found, compared with morphine or gabapentinoids, it had equivalent or better robust analgesic efficacy in various rodent acute and neuropathic pain models. Notably, we verified that RFUS -949 did not induce opioid-like side effects, indicating its favorable safety profile. It also showed a desirable safety in the GLP mouse and Beagle dog toxicology studies. The SAD and MAD investigations of Phase I in healthy volunteers are ongoing and the preliminary data indicate the AEs of RFUS-949 are transient and mild.

Conclusions: In summary, RFUS-949 becomes a new efficacious option to the clinical pain management without the risks associated with traditional opioids, supporting the development of S1R antagonists as therapeutics for acute and chronic pain.

References: N/A

Presenting Author: Hao ZHOU
Submitting Author: Xin Fang

Senior Author: Xin FANG

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Qiang YIN: Ph.D - Yichang Humanwell Pharmaceutical Co. Ltd
• Luanyuan TIAN: Ph.D - Yichang Humanwell Pharmaceutical Co. Ltd
• Xijun SHENG: Ph.D - Yichang Humanwell Pharmaceutical Co. Ltd
• Min ZHANG - Yichang Humanwell Pharmaceutical Co. Ltd
• Zejian DING - Yichang Humanwell Pharmaceutical Co. Ltd
• Yao HE - Yichang Humanwell Pharmaceutical Co. Ltd
• Chengling LI: Ph.D - Yichang Humanwell Pharmaceutical Co. Ltd