Yinghong Li, PhD | Chinese Academy of Medical Sciences; Danqing Song, PhD; Xi Lu, PhD; Yonghua Liu, PhD; Xican Ma, PhD
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2025
Multidrug-resistant (MDR) Gram-negative bacteria pose a significant global public health threat. Compounding the issue, no drugs with novel mechanisms of action or new chemical scaffolds have been approved worldwide over the past four decades, leaving substantial unmet clinical needs. IMBZ18G, a Class 1 novel monocyclic β-lactam drug independently developed by our team, demonstrates outstanding in vitro and in vivo efficacy against clinically prevalent, intractable infections caused by MDR Enterobacteriaceae, and possesses favorable druggability profiles. Mechanistically, it simultaneously binds to penicillin-binding proteins 3 (PBP3) and 1B (PBP1B), and exhibits high stability against Class A, B, C, and D β-lactamases. IMBZ18G is currently undergoing Phase I clinical trials in China. Furthermore, its combination formulation with avibactam (a β-lactamase inhibitor), designated IMBZ19G, outperforms Pfizer’s newly approved aztreonam-avibactam for the treatment of severe infections caused by MDR Gram-negative bacteria, underscoring its extensive clinical application potential. Our future research efforts will focus on establishing price competitiveness ahead of its commercial launch by optimizing the synthetic process of IMBZ18G, and expediting the preclinical development of IMBZ19G to secure its Investigational New Drug (IND) application acceptance. This project is expected to provide a promising therapeutic option for the treatment of MDR Gram-negative bacterial infections, as well as novel insights into the underlying mechanisms, thereby improving the prognosis of patients with such infections.