Making your company go viral: Adaptive Phage Therapeutics

Issue 136 | July 23, 2021
15 min read
Capsid and Tail

This week, Kyle Jackson (PhD student at McMaster University) brings us a profile of Adaptive Phage Therapeutics, the clinical-stage phage biotech company commercializing the US Navy’s phage collection. This is the first in a new column Kyle will be writing, to help us keep up with the phage companies bringing phages closer to the clinic!

What’s New

Biochimpharm, a Georgian phage biotech company, has been awarded a $150,000 grant from the EU and the United Nations FAO to support production of PowerPhage, a phage cocktail product that targets Salmonella, E. coli and Shigella, for veterinary use. This grant, together with the $1M investment raised, is aimed to allow a 300% increase in the production of PowerPhage.

Biotech newsFunding news

Microviridae (a family of tiny ssDNA phages) tend to dominate human viromes, yet little is known about them. Paul Kirchberger (UT Austin) and colleagues published a new paper in PNAS describing how microviruses encode defensive hypervariable regions that confer superinfection exclusion by repurposing an essential viral structural component.

Phage defense systemsResearch paperSuperinfection exclusion

Luke Hillary (Bangor University, UK) and colleagues published a preprint on how diverse soil RNA viral communities have the potential to influence grassland ecosystems across multiple trophic levels. They identified 3,462 viral OTUs and assessed their spatial distribution, phylogenetic diversity and potential host ranges. The study represents an important step towards the characterization of terrestrial RNA viral communities and the intricate interactions with their hosts.

PreprintSoil viruses

Yicheng Xie (Texas A&M) and colleagues published a research article in Frontiers in Microbiology on differential phage efficacy in controlling Salmonella in cattle hide and soil models. They found that phage ability to plaque on a bacterial strain is a poor indicator of antimicrobial activity, but performance in liquid cultures is a better predictor. They also concluded that a phage capable of achieving bacterial reduction in one model is more likely to perform well in another.

Antimicrobial activityResearch paper

Daniela Staquicini (Rutgers Cancer Institute of New Jersey) and colleagues published a new paper in PNAS on the design and proof of concept of two phage-based, cold-free COVID-19 vaccination strategies. They show that aerosol vaccination with phage particles displaying short S protein epitopes, and subcutaneous vaccination with adeno-associated virus/phage particles carrying the entire S protein gene, both elicit systemic and specific immune responses in mice.
Paper | NSF Press release

COVIDPhage-based vaccinesResearch paper

Latest Jobs

Sponsored Ad Phage Biotech

Scientist: Phage Biologist

A&P Inphatec

Palo Alto, CA

A&P Inphatec, LLC is seeking an experienced bacteriophage biologist applicant to join our research and development team as a full-time Scientist. This individual will be responsible for characterizing the bacteriophages in A&P’s library, as well as developing new bacteriophage discovery and characterization techniques.
Bioprocess EngineerPhage based products
Intralytix (Columbia, MD) is seeking a bioprocess engineer to work on upstream generation of phage-based products in bacterial systems, including concentration/purification of phages, and drying of phage cocktails into solid format.

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!

A new ESCMID Study Group that will deal with phage therapy has been created: the ESCMID Study Group for Non-traditional Antibacterial Therapy (ESGNTA).

ESGNTA aims to explore non-traditional antibacterials including phage and phage-related products for therapy, as well as increase and support the knowledge in phage lysin and other protein research, and understanding carriers and applications optimal for use in clinical settings (ex: gel, nanoparticles, etc.).

You can visit the website of ESGNTA to learn more about its mission, objectives, and bylaws. Any ESCMID member can join (you can become an ESCMID member here) — please spread the word!

Many thanks to the ESGNTA inauguration committee: Prof. Ran Nir-Paz, Prof. Tristan Ferry, Dr. Patrick Soentjens, Prof. Zuzanna Drulis-Kawa, and Prof. Joana Azeredo, whose hard work resulted in the ESGNTA being created and accepted into ESCMID!

ESCMIDInfectious diseaseNew study groupPhage Therapy

ASM Microbe 2022 will be held on June 9-13, 2022 in Washington, DC. This is the biggest microbiology conference in the world, and we strongly believe that there should be a session dedicated to phage therapy, which we would like to propose to ASM. The deadline for Session Proposal submissions is August 5th, 2021.

We would therefore like your urgent feedback by July 29th, 2021, to help us prepare the proposal. Please let us know if you are aware of anyone else proposing a phage session. We need suggestions for speakers, topics or any other ideas that could help with the application and the session. We would also like to hear from anyone interested in helping to organize the session.

We’ve set up an online form for your input here. We welcome and appreciate all suggestions and offers of assistance!

Feel free to email Ben Burrowes about further questions/more info: ben@bbphage.com

ConferenceSeeking feedbackSession proposal

Africa Phage Forum #5 will be a talk entitled ‘Shaping P. aeruginosa phages by genome engineering’ by Diana Priscila Pires, PhD, postdoc researcher at CEB - Centre of Biological Engineering, University of Minho, Braga, Portugal.

Join us Friday, July 30, 2021 4pm GMT+1 / 6pm EAT. Register at https://apf.phage.directory!

Africa Phage ForumVirtual Event

You can now watch the recording of PHAVES #19: Phage therapy for difficult-to-treat infections in children, with Dr. Ameneh Khatami here on the Phage Directory YouTube channel — PHAVES playlist. Thanks to everyone who came out for this event!

PHAVESPhage TherapyVideo

Phage Phridays on Clubhouse released this recording of last week’s conversation with Josh Borin from the Meyer lab at UCSD, wherein they discuss his PNAS paper titled “Coevolutionary phage training leads to greater bacterial suppression and delays the evolution of phage resistance”.

Join Phage Phridays, hosted every Friday by Sabrina Green, Adriana Carolina Hernandez, and Jean-Paul Pirnay in the ‘Phage Club’ within the Clubhouse app!

Audio recordingClubhousePhage training

Making your company go viral: Adaptive Phage Therapeutics

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 is the first in a new recurring C&T column entitled ‘Making your company go viral’, conceived and written by McMaster PhD student Kyle Jackson, who will be profiling phage companies and reporting on trends in the phage biotech industry. Kyle has a unique background that crosses over between biomedical commercialization and phage biology, so we’re delighted to have him help keep us all up to date with the phage industry’s progress! Welcome Kyle to the C&T team!

First use of the US Navy’s phage library to treat a patient

In 2003, NIH scientist Carl Merril, MD published a consequential article in Nature Reviews Drug Discovery outlining the prospects of using phages as therapies in Western medicine. In 2010, the Biological Defense Research Directorate of the US Navy, part of the Department of Defense (DoD), began exploring these concepts in response to the growing threats associated with multidrug resistant pathogens. Over the next few years, they began developing a catalogue of phages that could be screened against emerging pathogens for rapid antimicrobial applications. This approach achieved a significant milestone in 2016 with the successful treatment of Tom Patterson, a critically ill A. baumannii-infected patient. Patterson’s intervention represented one of many successful compassionate use applications of phage therapy in modern medicine, both in the US and around the world.

APT acquires rights to US Navy’s phage catalogue

In recognizing a deeper need for the rapid deployment of phages into clinical settings, Adaptive Phage Therapeutics (APT) was founded in Gaithersburg, Maryland in late 2016 by Dr. Carl Merril and his son Greg Merril. In 2017, APT acquired the exclusive global rights to the US Navy’s phage catalogue, and expanded it into PhageBank™, now considered to be one of the largest and most detailed phage repositories in the world. APT’s objective is to optimize precision phage therapy so that phage therapy can be rapidly and cost-effectively deployed to critically-ill patients globally.

Growing to 93 employees and another $40 Million raised

APT is a privately held, venture capital-backed biotech company. With 43 employees and actively recruiting to fill 50 open jobs, it’s still considered relatively small. Nonetheless, APT has demonstrated its ability to raise impressive capital to finance its drug discovery pipeline, with total capital raised exceeding $90 Million including both investment and R&D contracts. On May 11th, 2021, APT announced their most recent close of $40.8M in a Series B round led by Deerfield Management Company. This financing will be focused on advancing their ongoing clinical trials and expanding their PhageBank™ library.

A look at APT’s investors to date

APT is supported by a diverse portfolio of investors, all of whom bring different expertise to the growing phage therapy space. Originally supported by the DoD, APT quickly attracted the attention of groups interested in advancing phage-based therapeutics. One of those investors includes Hackensack Meridian Health, a New Jersey-based network of healthcare providers with a focus on developing an integrated system to deliver more efficient healthcare services. Hackensack invested in APT in 2019 as part of their innovation program to develop novel therapeutics to combat growing healthcare challenges. The investment was in response to the urgent request from physicians who were frequently treating patients with multidrug resistant bacterial infections.

APT’s other major investors include TEDCO, a Columbia, MD-based, life sciences-focused business development firm, Alexandria Venture Investments, based out of San Francisco, California, and most recently Deerfield Management Company, a New York-based investment firm dedicated to advancing healthcare that manages $14 billion in assets.

APT’s research pipeline and clinical trials: three pillars

First pillar: PhageBank™ for treating bacterial infections

APT’s developmental pipeline includes three broad categories. Its central pillar is its PhageBank™. Currently, the technology is being used on compassionate use grounds and for several FDA IND-allowed clinical trials for prosthetic joint infections (PJI), chronic recurrent urinary tract infections (UTI), and chronic wounds that involve osteomyelitis – most notably diabetic foot ulcers.

PhageBank™ vs. prosthetic joint infections

On February 10th, 2021, APT announced FDA clearance of an IND to use PhageBank™ against PJIs. With this announcement, APT is sponsoring the development of a controlled clinical trial involving patients with PJI. They anticipate enrolling 78 participants in the study with an estimated completion date of May 2024. The study is designed to evaluate the efficacy of phage therapy against chronic prosthetic joint infections of the hip or knee involving one or two of the following organisms: Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus spp., Enterococcus faecium, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and/or Klebsiella pneumoniae. The study will also be comparing the use of phage therapy in conjunction with antibiotics against the standard of care of PJI: two-stage exchange arthroplasty in tandem with antibiotics. The trial is co-sponsored by the Mayo Clinic and done in collaboration with the University of Maryland.

PhageBank™ vs. urinary tract infections

APT’s efforts to treat UTIs are being spearheaded through their phase 1/2 clinical trial. APT announced in a press release on June 3rd, 2021 that they’d administered the first PhageBank™ dose of the trial to an enrolled patient. The trial represents the first study for intravenous and/or bladder instillation-administered use of the PhageBank™. The trial is evaluating the safety and efficacy of phage therapy against Escherichia coli or Klebsiella pneumoniae UTIs. With an anticipated enrollment of 156 patients over the course of the trial, it’s being primarily conducted at the James J. Peters VA Medical Center in Bronx, New York. Patients will be monitored for bacterial clearance or recurrence of the infection, and the trial will ultimately assist in confirming or modifying phage dosing regimens for future interventions. APT is hoping the results from this trial will lead to regulatory approval and a green light for larger clinical trials. These efforts are funded by a $14.2-Million advanced development contract in partnership with the DoD.

PhageBank™ vs. ophthalmic infections

On June 10th, 2021, APT announced a unique collaboration with Oyster Point Pharma, Inc. (Nasdaq: OYST), a clinical-stage biopharmaceutical company focused on treating ocular surface diseases. Under the partnership agreement, Oyster Point Pharma will be able to obtain exclusive licensing options and leverage APT’s PhageBank™ technology to target ophthalmic infections. If successful, these would be the first ‘evergreen antimicrobials’ to enter the ophthalmic market – an accomplishment that would further cement APT in the antimicrobial space.

Second pillar: A high-throughput platform for phage susceptibility screening

APT’s second pillar focuses on high-throughput screening of bacteria for phage susceptibility testing, which promises to simultaneously test hundreds of phage candidates selected from PhageBank™ and piece together a personalized therapy to meet the needs of the individual patient. At launch, the phage susceptibility testing will be offered worldwide as a service by Mayo Clinic Laboratories, and will enable rapid identification of patient-specific therapies. This means the system will be able to identify a single phage, or a collection of phages, and develop a cocktail that will be deployed to combat the infection. This project is a direct collaboration with the Mayo Clinic, where a proportion of the revenue generated from the service will be used to support the clinic’s not-for-profit mission in patient care, education, and research. The development of this platform is also supported through an advanced development contract with the DoD.

Third pillar: Phage-based COVID vaccines

APT’s final pillar stems from their response to the COVID-19 pandemic. APT has leveraged its expertise in phage engineering to design a modified phage that expresses SARS-CoV-2 epitope proteins on the capsid surface. They’re now exploring using the modified phage as a highly stable, easy to manufacture, orally-administered vaccine, and are currently evaluating their candidate in a phase 1 clinical trial to assess the safety, tolerability, and immunogenicity in healthy adults. Phage-based vaccines are not a new concept, but the success of this trial will further demonstrate their design flexibility and functionality as future vaccine candidates.

Concluding thoughts

Much has happened since 2016, when Tom Patterson’s life was saved by some of the phages that now make up APT’s growing PhageBank™. APT has since brought on considerable investment, is positioning its PhageBank™ as a treatment for multiple clinical indications (even moving into the COVID vaccine space!), and stands as an exciting company to watch!


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

Capsid & Tail

Follow Capsid & Tail, the periodical that reports the latest news from the phage therapy and research community.

We send Phage Alerts to the community when doctors require phages to treat their patient’s infections. If you need phages, please email us.

In collaboration with

Mary Ann Liebert PHAGE

Supported by

Leona M. and Harry B. Helmsley Charitable Trust

Crossref Member Badge