Pulmobiotics Highlights Nature Biotechnology Publication of Preclinical Data Demonstrating Clearance of Antibiotic-resistant Lung Infection
First ‘living medicine’ to treat antibiotic-resistant Pseudomonas aeruginosa infections in the lung, a leading cause of mortality in hospital settings
Data demonstrate treatment reduced lung infection and increased survival in preclinical models, and support advancement of ongoing research leveraging platform in other serious lung diseases, including lung cancer and asthma
BARCELONA, Spain – January 19, 2023 – Pulmobiotics SL, a biotechnology company pioneering novel live biotherapeutics for the treatment of lung diseases, and the Centre for Genomic Regulation (CRG), an international biomedical research institute of excellence whose mission is to discover and advance knowledge for the benefit of society, public health and economic prosperity, today announced the publication of preclinical results demonstrating that treatment using Pulmobiotics’ engineered live biotherapeutic significantly reduced antibiotic-resistant Pseudomonas aeruginosa infections in the lungs of mice, thereby improving survival rates, and dissolved biofilms formed on endotracheal tubes of patients with ventilator-associated pneumonia (VAP). These data highlight a promising new approach to treat antibiotic-resistant Pseudomonas aeruginosa lung infections, a leading cause of mortality in hospital settings, and could offer a potential alternative to the use of antibiotics that enable antibiotic resistance, a global public health crisis. Importantly, these data also support the application of Pulmobiotics’ synthetic biology research platform to discover and develop novel live biotherapeutics for the treatment of other serious lung diseases.
This novel treatment approach uses a strain of attenuated live bacteria genetically engineered to produce specific enzymes with activity against Pseudomonas aeruginosa and the biofilms it forms which help the bacteria evade the immune system and antibiotics. This publication is the first time data has been described for a live biotherapeutic for the treatment of lung infection caused by Pseudomonas aeruginosa. The results are published in Nature Biotechnology and this research is supported by the European Research Council through an H2020 project and “la Caixa” Foundation through the CaixaResearch Health Call.
“We have developed a battering ram that lays siege to antibiotic-resistant bacteria. The treatment punches holes in their cell walls, providing crucial entry points for antibiotics to invade and clear infections at their source,” said María Lluch, PhD, co-founder and Chief Scientific Officer at Pulmobiotics, Professor of Basic Sciences at the Universitat Internacional de Catalunya and co-corresponding author of the study. “This new treatment approach is working as intended, and, importantly, demonstrates strong activity against the difficult-to-penetrate bacterial biofilms. We believe these data represent a promising new strategy to address a leading cause of mortality in hospitals.”
Data demonstrate a signification reduction of Pseudomonas aeruginosa bacterial load in lungs of treated mice compared to controls. Histopathology assessment showed a significantly lower total score of lung lesions in lungs of treated mice compared to controls with less inflammation and less pneumonia indicating that treatment reduced Pseudomonas aeruginosa lung infection in the acute pneumonia mouse model.
In mice with acute lung infections, treatment doubled their survival rate. 50% of mice given the treatment survived after eight days, the time period given for an infection to clear, whereas only 25% of the untreated mice survived.
The treatment dissolved Pseudomonas aeruginosa biofilms formed on the surface of endotracheal tubes from VAP patients in the intensive care unit. Biofilms are clusters of bacteria that form impenetrable structures that are highly resistant to antibiotics. Treatment led to a significant reduction in Pseudomonas aeruginosa bacterial load with the Pulmobiotics treatment alone or in combination with ceftolozane/taxobactam antibiotics. These results demonstrate that the treatment has broad spectrum activity against biofilms formed by different multidrug-resistant Pseudomonas aeruginosa clinical strains.
There were no signs of toxicity in the lungs of mice after a single, high dose of the treatment, and the treatment was cleared in four days.
When tested as a prophylactic treatment against infection, the live biotherapeutic significantly reduced Pseudomonas aeruginosa in lungs of treated mice compared to untreated control mice
“Today’s publication is an exciting milestone for our company as it demonstrates the potential power of our live biotherapeutic platform in difficult-to-treat infectious diseases, as well as strong support for our belief that this approach can be applied to treat other serious lung diseases requiring continuous local delivery of a treatment” said Claudio Santos, PhD, Chief Executive Officer, Pulmobiotics. “We will continue to leverage our synthetic biology and microbiology engineering expertise to develop additional pipeline programs that address unmet clinical needs. Our recent funding awards from the European Union and Spanish government to advance treatments for additional lung diseases including NSCLC and asthma provide validation for this new modality and potential benefit for patients.”
The European Innovation Council has selected Pulmobiotics’ research platform as a potential breakthrough technology for the treatment of non-small cell lung cancer (NSCLC). The funding will support research aimed at advancing live biotherapeutics that can overcome resistance that many patients develop to treatment with immune checkpoint inhibitors. Pulmobiotics has also received funding from the Spanish Ministry of Science and Innovation’s “Public-Private Collaboration Projects” to develop novel treatments for severe asthma in a consortium with the Centre for Genomic Regulation (CRG) and the Institute for Research in Biomedicine (IRB).
About Pulmobiotics’ Live Biotherapeutic Treatment for Infectious Lung Disease
The live biotherapeutic was developed by modifying a bacterium, Mycoplasma pneumoniae, that is naturally present in the lung, removing its ability to cause disease and repurposing it to attack harmful microbes. It is designed to be administered alone or in combination with low dose antibiotics that would not work independently. The treatment offers an alternative to using high doses of antibiotics, which contribute to antibiotic resistance, a global public health threat. Unlike conventional treatments, an engineered bacterium may be able to deliver therapeutic molecules at the source of an infection without also adversely affecting healthy tissue, resulting in effective treatment with a low risk of side effects. Further preclinical testing and evaluation of the treatment is ongoing to support initiation of future clinical trials. The treatments being developed are designed to be administered using a nebulizer.
About Ventilator-associated Pneumonia
Ventilator-associated pneumonia (VAP) is a type of infection that affects critically ill patients who require intubation for breathing. Approximately 400,000 cases occur per year in the US and Europe and it is a significant cause of increased hospital stays and costs. The most common cause of VAP is Pseudomonas aeruginosa, a bacterium that accumulates on the surface of endotracheal tubes. In this environment, Pseudomonas aeruginosa forms biofilms that are extremely resistant to conventional treatments. To date, few treatments are available that can dissolve Pseudomonas aeruginosa biofilms, exacerbating mortality rates in intensive care units.
About Pulmobiotics SL
Pulmobiotics SL is a biotechnology company pioneering novel live biotherapeutics for the treatment of lung diseases. Using a proprietary microbial engineering and synthetic biology toolbox, the Company engineers bacteria to expose antigens or deliver therapeutic agents in a controlled, local and continuous manner. Pulmobiotics SL is currently using this technology to discover and develop novel treatments for respiratory diseases, which are among the most common causes of severe illness and death worldwide, and is exploring its application in other disease areas. Pulmobiotics is a spin-off company from the Centre for Genomic Regulation (Barcelona - Spain) founded by experienced entrepreneurs and funded by Invivo Ventures.
About the Centre for Genomic Regulation (CRG)
The Centre for Genomic Regulation (CRG) is an international biomedical research institute of excellence, created in July 2000. It is a non-profit foundation funded by the Catalan Government through the Department of Business & Knowledge and the Department of Health, the Spanish Ministry of Science & Innovation, the "la Caixa" Banking Foundation, and includes the participation of Pompeu Fabra University. The mission of the CRG is to discover and advance knowledge for the benefit of society, public health and economic prosperity. The CRG believes that the medicine of the future depends on the groundbreaking science of today. This requires an interdisciplinary scientific team focused on understanding the complexity of life from the genome to the cell to a whole organism and its interaction with the environment, offering an integrated view of genetic diseases.
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