Antibiotic therapy is typically successful for initial cases of CDI. However, 20%-40% of patients will suffer a recurrence, and the chance of additional episodes for these patients exceeds 40%. Currently available approaches for preventing CDI are hampered by high costs, inconvenient delivery (in most cases requiring either I.V. administration for traditional antibodies or bowel prep or enema for fecal microbiota transplant).
Lumen Bioscience, a clinical-stage biopharmaceutical company developing biologic drugs for highly prevalent diseases, today published research describing LMN-201, an investigational orally delivered biologic cocktail to prevent C. difficile infection (CDI). LMN-201 combines four therapeutic proteins—manufactured and delivered in the edible microorganism spirulina—that work synergistically to neutralize both the C. difficile bacterium and the toxin that causes its virulence.
The new paper, “Using antibody synergy to engineer a high potency biologic cocktail against C. difficile,” was posted on the preprint server bioRxiv pending peer review. It describes in vitro and in vivo data demonstrating that LMN-201 is highly effective at preventing CDI in two independent preclinical models of CDI. The research was carried out by Lumen scientists as well as leading researchers in the CDI field at independent research laboratories supported in part by funding from the NIH’s National Institutes of Allergy and Infectious Diseases.
The paper also reports an important advance in the science of antibody cocktail development that may enable far more potent antibody drugs in the future. The work illustrates how using quantitative analyses of antibody synergy to guide development can boost the potencies of cocktail therapeutics by thousands of fold. This aspect of the research has obvious implications for many disease targets beyond just C. difficile, including Lumen’s preclinical development programs in inflammatory bowel disease and cardiometabolic disease.
“LMN-201 establishes a new paradigm for safe and highly potent biologic cocktails for disease targets within the GI tract,” said Jim Roberts, Lumen’s co-founder and Chief Scientific Officer. “This approach has far-reaching implications for treating other GI-centric disorders with complex etiologies such as Crohn’s disease, ulcerative colitis, metabolic diseases, and celiac disease, where similar potency and scalability challenges have impeded the development of orally delivered protein therapeutics.”
The company also announced completion of Cohort 1 of its Phase 1 pharmacokinetic clinical trial of LMN-201. The primary goal is to evaluate the dissolution kinetics of enteric capsules designed to release LMN-201’s therapeutic proteins at or before the terminal ileum, where C. difficile becomes established in most patients. The trial met its primary endpoint for Cohort 1, indicating the capsules can successfully deliver LMN-201 where needed. Following completion of the study’s confirmatory Cohort 2 early next year, full analysis will be completed and published in a peer-reviewed journal.
