H3
Development of a Live Biotherapeutic Product to Promote Gut Decolonization of Multi-Drug Resistant and Pathogenic Bacteria
Prof. Till Strowig, Helmholtz Centre for Infection Research; Dr Lisa Osbelt-Block, Helmholtz Centre for Infection Research; Dr Marie Wende, Helmholtz Centre for Infection Research
Ascenion
Challenge
The global rise of multidrug-resistant (MDR) bacteria poses a major public health threat, causing about 1.2 million deaths and over US$3 trillion in annual losses. Gram-negative MDR pathogens like Klebsiella pneumoniae are especially dangerous (WHO, 2024) due to limited treatment options and high fatality rates. Most infections follow asymptomatic intestinal colonization with GN-MDRs, often acquired from hospitals, animals, the environment, or food. About 80% of GN-MDR infections stem from self-contamination in the gut. Antibiotics worsen the problem by disrupting the microbiota and selecting resistant strains, making them unsuitable for prevention. Currently, no effective strategy exists for targeted intestinal decolonization. This creates a major unmet medical need, particularly for high-risk patients (e.g., undergoing chemotherapy, immunosuppression, dialysis, or organ/abdominal surgery) with weakened microbiota and immunity accompanied with increased mortality and costs (~€27,000 per case) due to isolation, hygiene measures, and reserve antibiotics use.
Technology
We develop and clinically validate live biotherapeutic products (LBP) to treat intestinal colonization with Gram-negative multidrug-resistant and hypervirulent bacteria, particularly Klebsiella pneumoniae and E. coli. This first-in-class approach uses harmless, related bacteria (specific K. oxytoca and E. coli strains) delivered orally in acid-resistant capsules to competitively displace pathogens without harming the microbiome. The LBP strains also support recovery of beneficial anaerobes often depleted after antibiotic or immunosuppressive therapy. The active ingredients, a Klebsiella oxytoca and E. coli strain from healthy donors, have shown efficacy and safety in multiple preclinical in vivo models and can be produced cost-effectively. Next, we plan a Phase I adaptive clinical trial to demonstrate safety, determine optimal dosing, and collect initial efficacy data in colonized patients.
Commercial Opportunity
The results will also support the formation of our spin-off, Arvalus Therapeutics, to lead development, approval, and commercialization. Discussions with potential investors for an exit strategy and term sheet negotiations with HZI to secure the IP are already underway.
Development Status
The project is currently at TRL-5: Comprehensive in vitro and in vivo efficacy and safety data are available (seven peer-reviewed publications), complemented by GLP-like in vivo safety data from immunocompromised and immunocompetent mice. Additional dosage and toxicity studies are currently ongoing in pigs. A detailed study synopsis for a first-in-human trial has been prepared, and two patent families protect the invention. As a next big milestone we are conducting a scientific advice with BfArM in the upcoming month. In parallel, we focus on commercialization and company building and are in active negototiations for an exclusive license term sheet with the Helmholtz Centre for Infection Research.
Patent Situation
Two patent families protect our technology: 1. EP4011384A / US20240041950A1 – covers K. oxytoca and related species for GN-MDR gut decolonization. 2. EP24182102.4 / PCT/EP2025/060744 – covers combination therapies for gut decolonization using E. coli strains in combination with K. oxytoca against intestinal pathogens.
Further Reading
Osbelt L, Wende M, Almási É, et al. Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition. Cell Host Microbe. Published online October 4, 2021. doi:10.1016/j.chom.2021.09.003
