Lumen Bioscience reported groundbreaking results from the sentinel cohort of its RePreve Clinical Trial, where its investigational oral biologic LMN-201 achieved a 100% clinical cure rate for Clostridioides difficile infection (CDI). All 21 patients who completed the treatment regimen achieved initial clinical resolution, significantly outperforming the 80% cure rate observed in the active arm of the large MODIFY I and II studies (p << 0.001).
The Seattle-based company's LMN-201 is an oral biologic cocktail delivered in capsules, designed to be used alongside and following standard antibiotic therapy to improve clinical outcomes for C. difficile infection. The treatment is manufactured using Lumen's proprietary spirulina-based GMP manufacturing system.
Impressive Clinical Results
The sentinel cohort (Part A) of the RePreve trial showed remarkable efficacy with LMN-201. The 100% initial clinical cure rate (21/21 patients; 95% confidence interval: 85%-100%) represents a significant improvement over conventional treatments.
"Seeing zero failures after initial combination treatments and a low recurrence rate in this high-risk group is extremely encouraging," said Dr. George McDonald, consultant to Lumen and Emeritus Professor of Medicine at the University of Washington. "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."
Perhaps even more significant was the dramatic reduction in CDI recurrence. Only one of 21 patients (4.76%; 95% CI: 0.24%-23%) who completed the seven-day treatment of standard-of-care plus LMN-201 experienced CDI recurrence within 28 days. This compares favorably to the 26% recurrence rate (161 of 621 patients; 95% CI: 23%-30%) observed after standard-of-care alone in the MODIFY I/II trials, and the 14% recurrence rate (87 of 625 patients; 95% CI: 11%-17%) after standard-of-care plus bezlotoxumab treatment.
The sustained clinical cure rate through Week 4—defined as initial clinical cure plus prevention of CDI recurrence—was 95.2% for LMN-201 plus standard-of-care, compared to 59.5% for standard-of-care alone and 68.9% for standard-of-care plus bezlotoxumab in previous trials.
Dual-Action Mechanism
LMN-201 employs a novel approach to treating C. difficile infections. Brian Finrow, Lumen Bioscience cofounder and CEO, previously explained that the treatment was developed based on research showing that antibodies against C. difficile toxin B can neutralize the toxins similar to snake antivenom. LMN-201 combines this toxin-neutralizing capability with direct action against the bacterium itself.
"The formidable amount of novelty built into the Lumen platform comes with substantial challenges, but also the potential for great leaps forward in biologic drug development. We are seeing here the realization of that potential," said Dr. Jim Roberts, Lumen's cofounder and CSO.
Trial Design and Future Plans
The RePreve Trial has a two-part design. The recently completed Part A (sentinel cohort) was designed to confirm LMN-201's safety in high-risk individuals with CDI and optimize trial infrastructure. With these promising results, Lumen has now begun Part B (main cohort), a randomized, double-blind, placebo-controlled study that will enroll approximately 350 patients at research centers across the U.S.
Notably, the sentinel cohort results were achieved with only seven days of dosing. In the main cohort, the LMN-201 dosing window will increase from seven days to approximately 70 days (until eight 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.
"We are pleased that LMN-201 appears to be safe and well-tolerated in patients," added Finrow. "This was our first opportunity to observe LMN-201's effects in a clinical setting, in patients with active C. diff, and the absence of dose-related adverse events is reassuring."
Addressing a Significant Health Burden
CDI remains a serious and costly problem in healthcare. Nearly half a million cases occur in the U.S. each year, leading to an estimated 29,000 deaths and approximately $5 billion in hospital costs. Recurrent CDI drives much of this burden, with patients who relapse often requiring extended hospital care and potentially suffering multiple recurrences.
The U.S. Centers for Disease Control and Prevention lists CDI as an antimicrobial resistance "Urgent Threat," with growing concerns about resistance to vancomycin, the main antibiotic used in CDI treatment. Until now, efforts to improve CDI outcomes have had limited impact, due in part to high costs and inconvenient administration of other preventive therapeutics.
LMN-201 offers several potential advantages over existing treatments. Unlike bezlotoxumab, which was recently withdrawn from the market and carried a risk of heart failure, LMN-201 appears to be safe and well-tolerated. And unlike fecal microbiota transplantation (FMT) products, which are incompatible with antibiotics, LMN-201 can be used alongside standard antibiotic therapy to improve initial clinical cure rates.
The oral delivery method (capsules with no enema or "bowel cleanse" required) and scalable manufacturing process could allow for much broader potential use in routine CDI management.
Trial Recruitment Ongoing
The RePreve Trial main cohort is now recruiting patients. Researchers and potential participants interested in participating can email trials@lumen.bio or visit the official RePreve study webpage.
The work is supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Peer Reviewed Medical Research Program under Award No. HT9425-23-1-0959.
