— FDA clearance of investigational new drug (IND) application
— Initiation of multisite Phase 2 study in spring 2022
— Phase 1 pharmacokinetic study completed
Seattle, WA, April 18, 2022 – Lumen Bioscience, a clinical-stage biotechnology company developing biologic drugs for highly prevalent diseases, today announced clinical development progress for LMN-201, an investigational orally delivered cocktail to treat and prevent C. difficile infection (CDI). Achievements include FDA clearance of a planned Phase 2 study of LMN-201 and successful completion of a Phase 1 first-in-human study, which validated drug delivery of enteric capsules into the gut.
LMN-201 combines four therapeutic proteins—manufactured and orally delivered in the edible microorganism spirulina—that work synergistically to neutralize both the C. difficile bacterium and the toxin that causes its virulence. LMN-201 is the world’s first complex biologic cocktail to enter human clinical trials and represents a significant advance in the field of polypharmacology. Lumen recently published its pre-clinical data on LMN-201 on bioRxiv, pending peer review.
“We are excited to mark these clinical milestones for LMN-201 and advance the development of a candidate that offers the potential to impact recurrent CDI, a major health problem worldwide,” said Dr. Carl Mason, Lumen’s head of clinical research. “Lumen’s platform enables this novel approach of combining multiple therapeutic proteins into a single, low-cost, easily distributed and administered therapeutic. We are eager to advance LMN-201 into later stage clinical development.”
The Phase 2 trial (NCT05330182) will begin enrolling approximately 375 patients at sites across the United States. Physicians interested in participating are encouraged to contact Lumen’s clinical operations team at firstname.lastname@example.org. The double-blind, placebo-controlled study will evaluate the efficacy of LMN-201 in participants recently diagnosed with CDI receiving standard-of-care antibiotics.
The primary goal of the Phase 1 study of LMN-201 recently completed in Australia was to confirm 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, indicating the capsules can successfully deliver LMN-201 where needed. Initial analysis also confirmed the therapeutic proteins were bioactive upon release and demonstrated robust stability against gastrointestinal protease digestion over time, meeting the exploratory endpoints. Lumen plans to publish full study results in a peer-reviewed journal after complete data analysis.
About C. difficile infection
C. difficile infection (CDI) is the most common cause of health care-associated infections in U.S hospitals, where nearly half a million CDI cases occur each year. CDI is often considered a hospital-acquired infection, but community-associated CDI is on the rise and now comprises a majority of 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 and inconvenient delivery (in most cases requiring either I.V. administration for traditional antibodies or bowel prep or enema for fecal microbiota transplant).
LMN-201 is a cocktail of two classes of therapeutic proteins: the world’s first complex biologic cocktail drug. The first class is comprised of three antibody-like proteins that bind and neutralize the bacterial toxin that is the main cause of the diarrhea and other severe symptoms of CDI. The second is an enzyme protein that destroys the cell wall of the C. difficile bacterium itself. The product is orally delivered in capsules and shelf stable, facilitating ready distribution to broader patient populations than is feasible with most other interventions available or in development for CDI.
To facilitate accessibility to the broadest possible patient population, these monoclonal proteins are expressed and delivered within whole spirulina biomass, a type of blue-green algae widely consumed as a nutritional supplement that Lumen has repurposed as a GMP biomanufacturing host as described in Lumen’s recent paper in Nature Biotechnology. All four therapeutic proteins do their work without perturbing the patient’s healthy GI microbiome. There has always been a certain illogic in using antibiotics to treat C. difficile infection, which is usually caused by prior antibiotic damage to the GI microbiome. Rather than treating CDI, which in most patients is easily cleared with generic antibiotics, therefore, LMN-201’s primary purpose is to be delivered alongside and for a short period after antibiotics to prevent future bouts with CDI, a common side effect of antibiotics. Lumen recently published its pre-clinical data on LMN-201 on bioRxiv, pending peer review.