— Preclinical data demonstrate LMN-201’s potential for preventing disease in at-risk patients
— Lumen also announces successful Cohort 1 results in Phase 1 clinical trial
Seattle, WA, December 23, 2021 – 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.
About C. difficile infection
C. difficile is the most common cause of health care-associated infections in U.S hospitals, where nearly half a million CDI cases occur each year. Treatment costs are estimated to exceed $5 billion a year, but the true economic burden is far higher when lost quality-adjusted life years are considered. CDI is often considered a hospital-acquired infection, but community-associated CDI is on the rise and now comprises most cases in some regions.
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).
LMN-201 addresses the illogic of using antibiotics to treat CDI, which is often triggered by prior antibiotic damage to the patient’s microbiome. The product’s four therapeutic proteins are lab-made versions of molecules that nature has been refining for millions of years. The first class is comprised of three antibody-like proteins that bind and neutralize the bacterial toxin that is the main cause of diarrhea and other severe symptoms of CDI. The second is a single enzyme called an endolysin, which destroys the cell wall of the C. difficile bacterium itself without upsetting the patient’s healthy GI microbiome. It is derived from a molecular “battering ram” deployed by bacteria-invading viruses to punch holes in the cell walls of their bacterial hosts. The proteins are expressed and delivered within whole spirulina biomass, a type of blue-green algae widely consumed as a nutritional supplement.
The newly published research demonstrates that LMN-201 is highly effective at preventing CDI in animal models. In vitro analysis elucidates how the three antibody-like proteins in the product work synergistically: in combination they vastly exceed the ability of any individual protein to bind and neutralize the key C. difficile exotoxin TcdB, which prior research has shown to be the primary virulence factor in CDI. This combination was 300- to 3,000-fold more potent at neutralizing the most clinically prevalent TcdB toxin types than the FDA-approved monoclonal antibody therapeutic bezlotoxumab. The paper also explains how the therapeutic is further enhanced by combining the three toxin-neutralizing proteins with an endolysin enzyme.
Manufactured in recombinant spirulina, LMN-201 is delivered orally as a powder of dry spirulina biomass and is easily scalable, shelf-stable, simple to administer, and broadly neutralizing against all common C. difficile variants.
About the LMN-201 clinical development program
The open-label, exploratory trial underway in Australia is evaluating the delivery of LMN-201 via enteric capsules in the gut in healthy volunteers with mature ileostomies. Data from the initial cohort of 6 volunteers show that the capsules dissolved at the clinically relevant point in the GI tract, meeting the trial’s primary endpoint. Initial analysis also confirmed the therapeutic proteins were active upon release, meeting the exploratory endpoints.
Lumen is currently planning a Phase 2 trial to study the safety, tolerability, and efficacy of LMN-201 in preventing CDI recurrence. Physicians interested in participating in the Phase 2 study are encouraged to contact Lumen’s clinical operations team at email@example.com.