Overcoming barriers to phage commercialization: a conversation with leaders at Cytophage and BiomX

Issue 150 | October 29, 2021
18 min read
Capsid and Tail

This week, McMaster University PhD student Kyle Jackson interviews Cytophage and BiomX executives, who share phage therapy commercialization challenges and progress and a sneak peek into what they’ll present at Phage Futures.

You can also read this article on the Phage Futures Europe 2021 website here!

Phage Futures Europe (Nov 23-24, 2021 in Brussels, Belgium — in person!) will bring together biotech, pharma, academia and governmental bodies to help move phage therapy forward into clinically and commercially viable therapeutics.

For a 10% discount, code enter PD10 at checkout!

Phage Futures Europe

What’s New

David Picton (Durham University, UK) and colleagues published a new paper in Nucleic Acids Research showing the phage defence island of a multidrug resistant plasmid uses both BREX and type IV restriction for complementary protection from viruses. The authors also present the first structure of a GmrSD-family type IV restriction enzyme and acknowledge the work of 97 undergrads in isolating all 30 phages used in the study! Also check out Tim Blower’s thread about the work on Twitter!

MDR bacteriaPhage biologyResearch paper

We now know megaphages (phages with extremely large genomes) are ubiquitous, but before now, no complete marine megaphage had been identified. Slawomir Michniewski (University of Warwick) and colleagues published a new paper in ISME Communications showing a new family of “megaphages” abundant in the marine environment. They assembled >900 draft viral genomes from English Channel water, one of which encoded a novel 650-kB megaphage, making it one of the largest phage genomes assembled to date.

Marine phagesResearch paper

Carlos Martinez-Soto (Guelph Research and Development Centre, Canada) and colleagues published a new paper in Viruses describing PHIDA: a high throughput turbidimetric data analytic tool to compare host range profiles of phages isolated using different enrichment methods.

Host rangeResearch paperVirus tools

Dipesh Khanal (University of Sydney, Australia) and colleagues published a new paper in International Journal of Pharmaceutics on enteric-coated phage tablets for oral administration against gastrointestinal infections.

FormulationGut phagePhage TherapyResearch paper

The EMBO podcast has released a new episode entitled ‘the enemy of my enemy: the return of phage therapy’. This episode interviews Jonathan Iredell and Ameneh Khatami about their recent publication in EMBO Molecular Medicine on the seven-year-old girl who received phage therapy for a multidrug resistant Pseudomonas strain. Jessica Sacher also features in this episode, talking about how Phage Directory helped source phages for this case.

MDR bacteriaPhage TherapyPodcast

Latest Jobs

Marine MicrobiologyMarine phagesPhD projectPhage-bacteria dynamicsPost Doc
The Weitz Lab at Georgia Institute of Technology, Atlanta is seeking PhD students to work on phage-microbe dynamics or epidemic dynamics. The Weitz Lab are also hiring two post-doctoral researchers to investigate viral life evolution or the impacts of viral infection on marine microbial population dynamics.
PhD projectPhage biology
The Taylor Group at The Novo Nordisk Foundation Center for Protein Research (the University of Copenhagen, Denmark) is recruiting a PhD fellow in structural biology to use cryo-electron microscopy combined with functional techniques to study the mechanisms of contractile injection systems.
Gut microbiotaGut phagePhD project
The Raymond Lab at the University of Exeter, Cornwall (Penryn Campus) is seeking a PhD student to explore how to efficiently replace resistant Escherichia coli in the gut with harmless commensals by exploiting selective phage therapy.
BiofilmsResearch Fellow
The De Nobrega Lab at University of Southampton (Highfield Campus) is hiring a research fellow to create world-class interdisciplinary research and industry partnerships to deliver breakthrough science and technologies to control and exploit biofilms.
Marine MicrobiologyPost Doc
The Fish and Shellfish Diseases Unit at the National Institute of Aquatic Resources (DTU Aqua), Denmark is hiring a post-doctoral researcher to investigate prophylactic measures against F. psychrophilum including phage treatment as well as vaccinations.
Assistant ProfessorPhage-bacteria dynamicsVirology
The University of California, Los Angeles is hiring a Tenure Track Assistant or Associate Professor in Quantitative Virology. The ideal candidate will lead a creative and impactful research program in quantitative virology and/or pathogen-immune interactions and/or viral pathogenesis.
CRISPRPhage biologyPhage proteinsResearch Assistant
North Carolina State University, NC is hiring a research scholar to develop methods in phage engineering, recombinant protein production, and CRISPR technologies.

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

What an INCREDIBLE turnout on Twitter for #WorldPhageWeek this week! Thanks so much to all who have participated in our daily prompts — we’ve learned so much about the phage community, how people got into phages, what their favourite phage papers are, favourite phage phacts, burning questions they wish they knew the answer to, etc.! If you haven’t been following, head to Twitter and search the hashtag #WorldPhageWeek, and prepare to find a ton of new super interesting phage people to follow!

This of course has been a contest (crafted straight from the mind of Stephanie Lynch!), and the winner (random draw among those who participated) will receive personalized phage art from the talented phage professor/artist @Ellie__Jameson… winners to be announced soon!

This is so exciting! Phage Directory’s new structured peer feedback platform, Instill Science, is now live, and the first few requests have been posted and replied to!

Can you help your fellow phage researchers by providing a second set of eyes on their work? If so, check out the active requests. Currently, Bharat Jhunjhunwala, Steve Abedon, Stephen Amankwah, Noutin Fernand Michodigni and Jan Zheng are looking for feedback or collaborators, ranging from feedback on a study on phage therapy and a phage book chapter, to help with experiments and tools, to those willing to have a conversation about phage databases.

Become an Instill member!

What does feedback look like? Spend 30 mins reading through and giving your first impressions and overarching thoughts on any given piece of work. Your contributions will be tracked and recognized, and you’ll be helping fellow researchers by sharing your expertise.

Thanks so much to those who have already responded to these requests and are working to provide feedback already: Betty Kutter, Urmi Bajpai, Tobi Nagel, Daniel Schwartz, Katharine Muscat, and Atif Khan! You are all amazing and we are so grateful for your support!

Submit your own request for help!

Instill SciencePhage DirectorySeeking feedback

Today on the Clubhouse Phage Phridays at 2PM Eastern, Jessica and Jan from Phage Directory will continue last week’s discussion on the State of Phage Survey results; come ask all your questions about what we found about who’s collecting which phages, where in the world, how many, and how they’re characterizing them!

If you missed out on past Phage Phridays on Clubhouse, head on over to YouTube to listen to recordings, like this recent session on phage derived antimicrobials with guest speaker Dr. Rob Lavigne.

Antimicrobial developmentClubhouse

Hello, I’m Asher (amehr22@dths.org)! I’m a high school senior in Los Angeles pursuing a project on phage therapy, and I’ve hit a massive roadblock in trying to order phages. I’m reaching out, hoping someone has info on how I can get them. I’m hoping to examine the efficacy of phage therapy in treating cystic fibrosis in _C. elegans (P. aeruginosa PAO1-GFP). From my prelim lit review, it looks like the following phages as a cocktail show effectiveness: Pseudomonas phages vB_PaeP_PYO2, vB_PaeP_DEV, vB_PaeM_E215, and vB_PaeM_E217. Does anyone have info about how to order one or all of them?

Seeking phage for research

Register now for the Southeast Asia Virtual Phage Workshop which will be held in March 2022 by the NGO Phages for Global Health. Scientists from lower and middle income ASEAN member states are invited to apply by Nov 6.

Phage workshops

Twitter call-out from Barbara Brenner; phages-to-patients: We are looking for experts to draft (inter-)national guidelines on phage therapy for medical doctors and clinics treating all aspects from “who can get it” over “how is it to be applied” to “is it legal” and “who pays”. Cordial invite to join the team.

Phage TherapyPhage Twitter

Overcoming barriers to phage commercialization: a conversation with leaders at Cytophage and BiomX

Profile Image
PhD Candidate
McMaster University, Hamilton, Canada
Skills

Molecular Biology, Biotechnology, Phage isolation, Phage Therapy, Phage-host interactions

Graduated from McMaster University with a BHSc in Biomedical Discovery and Commercialization. Specialized in strategic business development focusing on novel biologic therapeutics and translational research. I have consulted for several Life Sciences startup companies compiling market intelligence and advising them on their commercialization and regulatory pathways.

My research explores the use of phage therapeutics to combat microbiome-based infections. I investigate phage-based methods of modulating the gut microbiome to prevent opportunistic pathogens from colonizing and inducing inflammation. It is my goal to develop comprehensive preclinical models to assess the efficacy of phage therapy candidates for use in the gut microbiome environment.

This week, Kyle Jackson, a PhD student at McMaster University, brings us an interview piece featuring Michael Graham, Chief Financial Officer at Cytophage, and Assaf Oron, Chief Business Officer at BiomX. He sat down with each to talk about some of the work these companies are doing to commercialize phage therapy, which they will be presenting at the upcoming Phage Futures Europe conference in Brussels, Belgium.

You can also read this article on the Phage Futures Europe 2021 website here!

Michael Graham

Michael Graham is Chief Financial Officer at Cytophage, which is developing technology that can generate any type of phage in the lab, replacing that ‘search-in-nature’ process and accelerating the development and application of phages to prevent or treat infections.


Assaf Oron

Assaf Oron is Chief Business Officer at BiomX, which is developing natural and engineered phage cocktails designed to target and destroy bacteria that affect the appearance of skin as well as chronic diseases such as cystic fibrosis, inflammatory bowel disease, atopic dermatitis and colorectal cancer.

“With multiple companies developing phage therapies and several upcoming clinical studies, the likelihood of delivering viable phage-based therapies to the industry is higher than ever before” — Assaf Oron, Chief Business Officer, BiomX

Prior to the COVID-19 pandemic, the World Health Organization estimated that by 2050, approximately 10 million people would die annually due to antimicrobial resistant (AMR) infections. During the pandemic, reports indicated staggering misuse of antibiotics by physicians and patients alike thinking it would be able to treat COVID-19 infections. This further misuse over the last two years is expected to exacerbate the established AMR crisis and reinforces the need for novel solutions.

Phage Futures Europe 2021 is slated to kick off on November 23rd and will bring together leaders in academia, regulatory, and industry to discuss the future of bacteriophages in a world where commonly used antibiotics are becoming less and less effective. The conference’s theme this year focuses on translational bacteriophage research and the commercialization of phage-based therapeutics.

The global market for phage-based companies has grown exponentially in recent decades. These companies are designing novel strategies to alleviate the burden society has placed on conventional antibiotics.

Cytophage is a synthetic biology phage-based company out of Winnipeg, Canada. Dr. Steven Theriault, Cytophage’s Chief Executive Officer, will be presenting at Phage Futures Europe on their innovative technology and its impact in Canada’s agricultural sector. Cytophage was the winner of the 2018 Nutreco Feed Tech Challenge and was the recipient of the TechConnect 2019 Defense Innovation Award. They are a leader in developing targeted treatment strategies to minimize antibiotic usage in livestock, or in the case of the Canadian market, fill an immediate need due to antibiotic usage being banned.

“A lot of questions [concerning the commercialization of phage] are how do you make them widely available? How do you make them cost effective? How do you improve their therapeutic outcome?” explains Michael Graham, Cytophage’s Chief Financial Officer. “Our whole technology is [about] overcoming the inherent weaknesses of natural phages.”

Natural phages present many commercial opportunities for companies, whether that be in the therapeutic, diagnostic, or even agricultural spaces. But there are key disadvantages to natural phages that investors simply cannot overlook.

“Some natural phages have an incredible shelf life, and some have a very poor shelf life. Unfortunately, when you’re looking for natural phages, you’re hoping to find that needle in a haystack that doesn’t have toxic genes, isn’t lysogenic, has to be shelf stable, and has to target your bacterium [of interest].” — Michael Graham, Chief Financial Officer, Cytophage

These are the key traits that need to be considered when companies are designing products based on phages. If you took the conventional approach of trying to find natural phages (i.e., a “Phage Hunt” – screening environmental samples against your target bacteria), it could take a while!

“There are 14 serotypes of E. coli that we target, and if you looked for natural phages, you would likely need 14 different phages in a single product to target that collection of bacteria. Meaning you would need to replicate a phage hunt 14 times, which is obviously extremely expensive and time-consuming.” says Graham. “Finding 14 different phages [that overcome those aforementioned barriers] would be a miracle.”

In response to these barriers, Cytophage has developed their core platform around the idea of modifying their phages to express desirable traits that minimize, or even eliminate, deleterious off target effects (resistance, lack of phage infectivity in vivo, etc.).

“We developed a platform where we start with a [base] phage with entrenched properties and are able to extend the host range [of the modified phage] and change the binding domain so that [the modified phage] binds more serotypes of the same species.”

Separately from expanding the host range specificities, Cytophage is able to remove certain genes from the phage, thereby preventing the incorporation of its genome into the host cell, which could lead to lysogeny and resistance. Ultimately, this level of modification to the phage is expected to significantly reduce the inevitable phage resistance that is often cited as a barrier to phage therapy adoption.

“If the phages bind, they kill. We are also able to predict mutants from those phage-bacterial interactions and can mitigate those risks of resistance” explains Graham.

Using these modified phages, Cytophage has managed to develop patented products that are able to target a wide variety of bacterial species including Escherichia coli, Salmonella, Clostridium perfringens, among others. They are hoping to have these products approved for commercial use, with specific focus on agricultural applications, in the near future.

According to Graham, at Phage Futures Europe 2021, you can expect to hear Dr. Steven Theriault, Cytophage’s Chief Executive Officer, talk about the exciting trial results that have been obtained from testing their cocktail solutions on poultry. You can also expect to hear future goals and targeted treatments from this Canadian synthetic biology company.

Aside from the agricultural implications of phages, the most common application people tend to gravitate towards is phage therapy in a medical context. Although much attention has been placed on finding solutions for acute infections, many phage-based companies have begun pivoting to treat chronic infections.

“Our focus is targeting chronic conditions” says Assaf Oron, Chief Business Officer at BiomX – an Israel-based clinical-stage phage therapy company – and speaker at this year’s Phage Futures Europe conference. “Our pipeline consists of multiple indications including acne, atopic dermatitis, inflammatory bowel disease (IBD) and cystic fibrosis.”

Last year BiomX had positive results from a phase 1 cosmetic clinical study where they used a proprietary phage cocktail, BX001, to target Cutibacterium acnes. They are expecting results from their follow-up phase 2 cosmetic clinical study in the coming weeks.

Additionally, BiomX wrapped up a successful phase 1a clinical study evaluating the pharmokinetics of BX002, an additional phage cocktail, in healthy volunteers, with the ultimate goal of treating potential pathogenic bacteria residing in the gut that may play a role in the onset and exacerbation of IBD.

“We hope to begin moving into larger phase 1/2 trials next year in IBD, cystic fibrosis and atopic dermatitis, so we expect this to be an exciting year” describes Oron. “We look forward to sharing these exciting results at Phage Futures Europe”.

BiomX is a global leader in phage therapy applications. Since their inception, they have been working strategically with hospitals and universities to advance phages’ clinical adoption and make it more accessible to the general public; a focal point of their message for Phage Futures Europe 2021.

“Phages were discovered a hundred years ago, and often people ask why we haven’t seen any phage-based therapies yet. What people need to know is that today there is both technological maturity and a growing unmet need, with increasing resistance to antibiotics, that could allow this new modality to become viable”.

When it comes to using phages as therapeutic tools, concerns regarding the patentability of phage therapy have historically been raised as a barrier to its adoption. However, Oron sheds an optimistic light here, explaining some of the ways BiomX has navigated this:

“We have been building a growing intellectual property portfolio to protect our phage cocktails”, explains Oron, “1) we sometimes apply synthetic biology, which allows a new composition of matter, and 2) all of our products are combinations, or cocktails, of phage, which have unique complementary properties that could be protected very similarly to the approach taken by microbiome companies developing products based on consortiums of natural bacteria, which build a patent portfolio to protect those combinations. Many of these principles also apply to our phage cocktails”.

BiomX holds patents for many of their phage products in major markets around the world including the United States, China, Canada, the European Union, and Australia.

“We’ve invested millions of dollars into developing phage assays and computational tools to optimize our phage cocktails to have complementary features such as host range, addressing resistance and biofilm penetration. These capabilities have also helped make our patent claims stronger.”

To hear more about how Cytophage, BiomX, and dozens of other key leaders in the phage field are moving toward translation of phage research and technologies, check out this year’s Phage Futures Europe Conference!

This issue was produced in collaboration with Kisaco Research to promote their upcoming Phage Futures Europe 2021 event.

Phage Futures Europe (Nov 23-24, 2021 in Brussels, Belgium — in person!) will bring together biotech, pharma, academia and governmental bodies to help move phage therapy forward into clinically and commercially viable therapeutics.

Grab your ticket for the conference, where Assaf Oron (CBO, BiomX) and Steven Theriault (CEO, Cytophage) and many more phage biotech professionals will give an overview of the latest progressions in the clinical landscape for phage-based application!

For a 10% discount, enter code PD10 at checkout!

Phage Futures Europe 2021

Many thanks to Atif Khan and Stephanie Lynch for finding and summarizing this week’s phage news, jobs and community posts!

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