Issue 213
CreatiPhage – The Pioneer in China
Adam Yang, an intern at Shanghai Institute of Phage, interviewed the co-founder of CreatiPhage, Nannan Wu. CreatiPhage is the first company applying phage therapy to humans in China, and seeks to promote the overall development of phage therapy regionally and globally.
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Urgent need for Klebsiella phages for patient in the UK
We are urgently seeking Klebsiella phages for patient in the UK.
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Updates
BiomX Inc. announced positive results from Part 1 of the Phase 1b/2a trial evaluating their novel phage cocktail, BX004, for the treatment of chronic pulmonary infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis.
In a new paper in Viruses, Sandrine Le Guellec and colleagues describe a preclinical study involving macaques to predict the efficacy of delivery of nebulizer-administered Pseudomonas aeruginosa phages during mechanical ventilation. They found that the lung deposition of viable phage particles ranged from 6% to 26% of the phages loaded in the nebulizer, and that 1 × 10^9 PFU/mL was an efficient dose.
In a new paper in Food Microbiology, Marta Volpi and colleagues report on a full-scale industrial trial to evaluate the efficacy of a commercial phage product to reduce the prevalence of naturally occurring Salmonella on pork carcasses. They found that phage application allows for approximately 79% reduction of Salmonella-positive carcasses.
In a new paper in Nature Microbiology, Charles Dulberger and colleagues show that the mycobacterial nucleoid-associated protein Lsr2 is required for productive mycobacteriophage infection.
A new paper in PNAS by Bin Li and colleagues discusses how viruses require the small polyamine spermidine to replicate normally, in part due to its important role in ribosomal translation. They found genes in many phages and eukaryotic viruses encoding enzymes that produce spermidine or homospermidine, supporting an important role of spermidine in virus biology.
Jobs
Postdoctoral Appointee-Bacteriophages for Gut Microbiome Manipulation at Sandia National Laboratories in Livermore, California
Are you looking to do creative research that addresses major challenges such as public health, climate change, and energy security Sandia/California’s System Biology Department is seeking a hardworking and dedicated molecular biology postdoctoral appointee to join a multidisciplinary team using microbiology, molecular and synthetic biology and bioinformatics methods to engineer phages to deliver genes to targeted bacteria in a mouse gut microbiome.
Research Scientist at A&P Inphatec in Palo Alto, CA
A&P Inphatec, LLC has commercialized the first product to treat Pierce’s Disease in grapevines. Our unique solution utilizes bacteriophages to target and kill the bacteria at the source of the problem – giving wine growers an organic and sustainable solution to a rising threat in California. A&P Inphatec, LLC is seeking an experienced microbiologist applicant to join our research and development team as a full-time Research Scientist.
We are looking to hire a part time laboratory technician with a background in microbiology; experience with clinical samples or phages is a plus but not required. We are a highly translational team involving close connections with clinicians & patient samples. Tasks would include standard microbiology techniques, working with phages (sensitivity testing, amplification, production), clinical sample processing, and routine laboratory maintenance. Please send CV to shawna.mccallin@balgrist.ch
We are looking for a highly motivated & collaborative postdoc to work in our translational team of clinicians & researchers at 80-100% for 1 yr on our clinical phage therapy projects for the treatment of UTIs. Experience with phages & in cell culture/microscopy; past experience with clinical samples is a plus. Tasks include phage sensitivity testing, analyzing clinical samples & characterization of interactions between phages & the urinary tract. Please send CV to shawna.mccallin@balgrist.ch
The University of Edinburgh is seeking a PhD student to study how the globally disseminated multi-drug resistant E. coli ST131 resists phage treatment while infecting the mammalian bladder, using a pig model of urinary tract infection (this is a fully funded, industry sponsored PhD position available to start before July 2023).
The Center for Innovative Phage Applications and Therapeutics (IPATH) at The University of California, San Diego is seeking a Postdoctoral Fellow or Project Scientist to help further their efforts to develop a collection of phages that kill human pathogens and to characterize this collection through sequencing and other analyses.
The University of Sheffield is looking for a student to join their research team and work on the development of phage therapy for use in AMR Diabetic foot infections.
Phagos is a French biotech company that is looking for lab technicians in microbiology and molecular biology.
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Our @PhageFiles podcast is finally here! Tune in on Spotify, Google Podcasts, Deezer and Amazon Music to listen to our first episodes. In our podcast we will discuss all things phage. You will hear from researchers and entrepreneurs interested in different aspects of phage biology. But first, we will tell you about the fascinating history of phage discovery.
We would like to thank @Ellie_Jameson for our beautiful phage mini versions. Check out more of Ellie’s artwork here!
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ESCMID (European Society of Clinical Microbiology and Infectious Diseases) is hosting a hands-on course on phage therapy 25 - 27 July 2023, Brussels, Belgium) -- register by 06 June 2023 (25 spaces only!).
Adam: Can you briefly introduce yourself and what prompted you to dive into phage research?
Nannan: I have graduated with a virologist PhD from École Normale Supérieure de Lyon, and I currently work in Shanghai Public Health Clinical Center (SPHCC), a hospital specialized in infectious disease. With most advanced equipment and edge-cutting researchers, SPHCC has one of the best research platforms exploring novel treatments against antimicrobial-resistant bacterial infection. Our team particularly focuses on phage therapy and believes that phage therapy will become an essential means to combat rapidly evolving antimicrobial-resistant bacteria. While there is a high volume of clinical demand in phage therapy, it needs urgent improvements, modifications, and standardizations. Therefore, I joined the Shanghai Institute of Phage as one of the co-founders in 2017. Being approved by the Ethics Committees in 2018, in SPHCC and Zhongshan Hospital Fudan University, we have launched the first clinical study of phage therapy in China. In the following years, we have designed individualized phage therapy for almost a hundred patients with an efficacy of over 70% and published several case research. During the clinical practice, we experienced challenges such as the low coverage rate of phage and the emergence of bacterial anti-phage resistance, and these prompted us to explore the underlying mechanisms and corresponding countermeasures. Despite the rapid advancement in phage research, there are still various interesting areas to explore given the diversity of bacteria and phage. For instance, we published the first phage therapy against secondary bacterial infection in four COVID-19 patients, and the first-in-human treatment using an RNA phage against Pseudomonas aeruginosa pneumonia. Through phage therapy, saving patients who were declared untreatable previously brings me tremendous sense of responsibility, honor, and accomplishment.
Adam: When was CreatiPhage founded and what is the company’s goal? Nannan: Since 2021, the volume of patients seeking for phage therapy has been increasing steadily, and the clinical trial could no longer satisfy the growing demand. Based on the experiences we accumulated through previous practices, we believe that now it is the time to introduce commercial funds to fuel standard research & development of phage therapy. Such a standardization will facilitate the approval process of commercial phage therapy, thus benefiting a broader range of patients. After being recognized as an outstanding project in first National Revolutionary Technology Competition organized by the Ministry of Science and Technology of China, we were prompted to found CreatiPhage (创噬纪). Being a pun in Chinese, the name describes our goal: to create a new era of phage. We aim to overturn the AMR crisis by developing innovative drugs and individualized therapies with our cutting-edge phage & bacteria resources.
Adam: What products does CreatiPhage provide now to meet its goals? Nannan: Right now, all our products are in developing or pre-clinical stage. We have two product strategies. The first one is to produce broad-spectrum phage cocktails against bacteria with ‘relatively low’ heterogeneity such as gram-positive Staphylococcus, Enterococcus, and gram-negative Acinetobacter baumannii. CreatiPhage is currently developing an extended-spectrum phage cocktail against Carbapenem-resistant A. baumannii (CRAB), covering all the tested CRAB clinical strains. For bacteria with high heterogeneity, such as gram-negative Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, we applied the second strategy to achieve broad coverage by using multiple cocktails of natural phages or a particular extended-spectrum cocktail of engineered phages. For example, CreatiPhage has designed three cocktails to cover all clusters of clinical MDR Klebsiella pneumoniae strains. We are also developing a broad-spectrum cocktail against P. aeruginosa with genetically engineered phages.
In addition, I want to mention the different approval policy of personalized treatment between China and the U.S. In China, the process begins with medical institutions filing Restrictive Medical Technology application to provincial Municipal Health Commission. Therefore, CreatiPhage collaborates with top medical institutions like Zhongshan Hospital, SPHCC, and Jiahui Health to develop personalized phage therapy against the most common ESKAPE infections. CreatiPhage provides phage libraries, high-throughput phage susceptible screening, and GMP standard phage preparations.
Adam: Is CreatiPhage currently running any trial for new products? Nannan: CreatiPhage have three pipelines for innovative drugs and one pipeline for personalized treatment. Among them, two have already entered the preclinical stage. One is the extended-spectrum, natural phage cocktail against CRAB pulmonary infections, and the other is the wide-spectrum, natural phage cocktail against epidemic MDR K. pneumoniae urinary tract infections. The synthetic phage cocktail treating P. aeruginosa infection is in the laboratory developing stage. The personalized phage therapy pipeline provides customized phages from established phage libraries to target ESKAPE infections in multiple sites, and we plan to file the Restrictive Medical Technology application to Shanghai Municipal Health Commission in the second quarter of 2023.
Adam: What do you think makes CreatiPhage unique? Nannan: We must first address that it is the unique characteristics of phage that makes CreatiPhage outstanding in combating bacterial infection compared to many other companies that focus on traditional antibiotics. In comparison to our counterparts exploring phage therapy, we excel in having ample experiences and unparallel resources and technologies accumulated through five years of phage therapy administration in human.
In regarding to CreatiPhage itself, we are a team of determined, aspiring, and professional members. We have eminent medical institutions as long-term partners. We have complete bacteria libraries and phage libraries, as well as their corresponding databases. We are also distinguished by our technologies such as phage-bacteria database building, high throughput phage screening and genetic manipulation of phage, allowing us to develop broad-spectrum phage cocktails and precise phage therapies to handle the most challenging bacterial infections.
Adam: What role do you think CreatiPhage will play in the phage therapy market locally and globally? Nannan: CreatiPhage is the first company applying phage therapy to human in China, and its founding members are the most influential Chinese phage researchers. Locally, CreatiPhage just sponsored the fifth China Phage Therapy Conference and became the vice president unit of Alliance Phage of China. Given the rapid development of innovative drugs, the revolutionary changes in approval policies, and the huge market volume in China, CreatiPhage aims to become a unicorn company in phage therapy and integrate all related resources to promote the development of phage industry in China. Globally, CreatiPhage has a business mode similar to Adaptive Phage Therapeutics (APT), which is a rapidly expanding, model company in the field. Although CreatiPhage is founded later than our predecessors like APT, we are more familiar with the clinical needs and solutions based on our previous experiences in hospitals. At the same time, CreatiPhage is actively preparing for overseas clinical trials, and we look forward to collaborating with more companies to come up with more effective and safer anti-bacterial means to cope with the urgent antibiotic resistance crisis.
Additional Links, Readings, and Notes
- CreatiPhage Website (http://cphage.com/) [Chinese]
- Alliance Phage China does not currently have a website yet as it was just founded in November 2022 during the fifth China Phage Therapy Conference to connect all the major institutions working with phage therapy
- Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients
- Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae
- Heterogeneous Klebsiella pneumoniae Co-infections Complicate Personalized Bacteriophage Therapy
- Potential of Therapeutic Bacteriophages in Nosocomial Infection Management
Adam Yang
Worked with various E. coli strains and cultured coliphage T4 to target those strains in an independent research project. Wrote a general review article about phage therapy. Currently studying the potential of using phage to address secondary bacterial infection in COVID-19 patients under some professors help.