Investigational Oral Biologic Achieves 100% C difficile Clinical Cure in Preliminary Cohort

Today, Lumen Bioscience reported that its investigational oral biologic, LMN-201, achieved a 100% clinical cure rate of Clostridioides difficile infection (CDI) in the sentinel cohort (part A) of its RePreve clinical trial. All patients (21 of 21; 95% CI, 85%-100%) achieved initial clinical resolution, significantly outperforming (P < .001) the 80% initial clinical cure rate (625 of 781; 95% CI, 77%-83%) observed in the active arm of the large MODIFY I and II studies.¹

“Seeing 0 failures after initial combination treatments and a low recurrence rate in this high-risk group is extremely encouraging. It suggests that LMN-201’s tandem mechanism—targeting both the C difficile bacterium and its toxin—can improve outcomes, as it did in preclinical studies,” George McDonald, MD, emeritus professor of medicine at the University of Washington, said in a statement.¹

McDonald acknowledges the small cohort size but notes that the clinical cure rate is a rarity. “While our sample size is limited, such an outcome gives us confidence as we move forward,” he said. “It’s a promising sign, suggesting that LMN-201 could significantly improve patient outcomes and reduce recurrence—the holy grail in C difficile management.”¹

Only 1 of 21 patients (4.76%; 95% CI, 0.24%-23%) who completed 7 days of standard of care (SoC) plus LMN-201 experienced CDI recurrence within 28 days compared with 161 of 621 patients (26%; 95% CI, 23%-30%) who experienced recurrence after SoC alone in MODIFY I/II and 87 of 625 patients (14%; 95% CI, 11%-17%) after SoC plus bezlotoxumab treatment in MODIFY I/II within the same period. Of the 21 participants in the RePreve trial sentinel cohort who completed 7 days of LMN-201, 16 received vancomycin, 4 fidaxomicin, and 1 metronidazole.¹

LMN-201 is delivered in capsules and is intended for use with and following antibiotics to improve clinical outcomes for C difficile infection. It is made with Lumen’s proprietary spirulina-based Good Manufacturing Practice system. In a previous interview with Contagion, Lumen Bioscience cofounder and CEO Brian Finrow explained that LMN-201 was developed based on former research from Massachusetts Biotechnology Council and Merck on the creation of an antibody against C difficile.^1,2

“What they found is that if you make an antibody against the C difficile toxin—the disease in humans is mediated by this toxin called toxin B—if you make an antibody, it'll neutralize the toxins just like snake antivenom,” Finrow said.²

These sentinel cohort results were achieved with only 7 days of dosing. In the RePreve trial’s main cohort (part B), the LMN-201 dosing window will increase from 7 days to approximately 70 days (until 8 weeks after initial clinical cure). This extended treatment duration aims to provide protection throughout the period of greatest risk for CDI recurrence: the weeks immediately after antibiotic use when the healthy commensal microbiome naturally re-engrafts.¹

With the sentinel cohort now completed, Lumen has begun part B (the main cohort). This pivotal phase is a randomized, double-blind, placebo-controlled study that will enroll approximately 350 patients at research centers across the US. Participants will be randomly assigned 1:1 to receive either LMN-201 or a placebo—each alongside standard antibiotic therapy—to rigorously evaluate the drug’s efficacy in a larger population. The primary end point is “sustained clinical cure” (initial clinical cure plus no recurrence at 12 weeks) relative to placebo.¹

The RePreve trial main cohort is now recruiting. For investigators and potential participants interested in participating, they can email trials@lumen.bio or visit the official RePreve study webpage.

References
1. Lumen Bioscience’s LMN-201 achieves 100% initial C. difficile clinical cure in preliminary cohort of RePreve trial. Lumen Bioscience. April 3, 2025. Accessed April 3, 2025. https://www.lumen.bio/2025/04/02/lmn-201-preliminary-cohort-repreve-trial/
2. Parkinson J. Investigational C diff antibody takes novel mechanism of action approach. Contagion. July 14, 2023. Accessed April 3, 2025. https://www.contagionlive.com/view/investigational-c-diff-antibody-takes-novel-mechanism-of-action-approach