Podovirus

"When I first started, I was treating anything and everything in terms of ‘this is highly drug resistant and it's failed’. But I think I have a clearer idea now, at least clinically, where I think phage would be beneficial, rather than all comers.”

What does it take to achieve an 85% success rate with phage therapy? We talk to Dr. Saima Aslam, MD, MS, a Professor of Medicine at UC San Diego and the clinical lead of IPATH (Center for Innovative Phage Applications and Therapeutics), about her strategies for successful phage treatment. 

Since 2017, Dr. Aslam has treated many patients with phages, and learned crucial lessons about patient selection, trial design, and the importance of collaboration between clinicians and phage researchers. We explore how her approach has evolved from "treating anything and everything" to targeted strategies, why early clinical trials struggled, and her exciting NIH-funded placebo-controlled trial for recurrent UTIs in kidney transplant patients. 

The conversation covers practical implementation challenges and lessons for phage therapy practitioners, and discusses her vision for a centralized US phage repository and manufacturing center to reduce the current 6-12 month delays in accessing treatment.

Here's a taste of what we covered:

1. 🧫 Why patient selection is crucial: not all infections benefit equally from phage therapy

2. 🏥 Why phage scientists and clinicians must work together from day one

3. 🧪 Learning from early studies to create pragmatic, enrollable protocols

4. ⌛ The challenge of long-established biofilms in chronic infections like LVAD bacteremia

5. 💉 Why recurrent UTIs in transplant patients represent the "lowest hanging fruit"

6. 🔬 How Dr. Aslam designed her NIH-funded clinical trial for recurrent UTIs in kidney transplant patients

7. 🌐 The urgent need for centralized phage production in the US to reduce treatment delays

Chapters:

00:00 Introduction to Phage Therapy and Dr. Saima Aslam

02:11 Early Experiences and Lessons in Phage Therapy

05:27 Criteria for Patient Selection in Phage Therapy

09:14 Challenges in Phage Therapy: Availability and Effectiveness

12:31 Collaboration and Research in Phage Therapy

24:08 Bottlenecks in Phage Therapy Development

36:07 Future Directions and Hopes for Phage Therapy

Learn more:

Saima’s team is now enrolling for their kidney transplant phage clinical trial! (https://clinicaltrials.gov/study/NCT06409819)

A recent paper by Saima and her team:

Phage Therapy in Lung Transplantation: Current Status and Future Possibilities (https://pubmed.ncbi.nlm.nih.gov/37932113/)

"It's unacceptable to just tell this poor patient, there's nothing I can do to help you... That's when I thought, okay, well, what about kind of pushing the boundaries a bit here and thinking about phage therapy?" - Dr. Marisa Azad

Join us for an inspiring conversation with Dr. Marisa Azad, a clinician-scientist at The Ottawa Hospital who is pioneering the treatment of chronic infections using phage therapy. Dr. Azad shares her journey from microbiology PhD to orthopedic infectious disease specialist, and how a desperate patient case led her to become the first in Canada to use phage therapy for prosthetic joint infections.

Here's a taste of what we covered:

1. 🦠 The challenges of treating orthopedic infections, and how the problem is typically being dealt with in Canada (hint: MULTIPLE repeated surgeries for years is normal)

2. 🧪 How Dr. Azad navigated regulatory hurdles to bring phage therapy to Canada, and what it was like working with Health Canada (Canada's FDA) to get approval

3. 💉 Insights on phage administration and patient immune responses: what she's learned and what barriers she sees

4. 🔬 The importance of collaboration in advancing phage therapy research, and what's left for researchers to figure out

5. 👩‍🔬 How crucial it is to support women in science and medicine, still in 2025, especially in innovative fields that require taking steps your field isn't taking (which require extra bravery and support systems!)

6. 🏥 Bridging the gap between basic science and clinical practice: how Dr. Azad weaves together both ways of thinking, all with patient benefit as her central driver

You can also watch the episode on YouTube: https://youtu.be/5TKhgFplvfU

Want to learn more?

- CBC (Canada's national news outlet)'s coverage of Dr. Azad's successful case, and how patient Thea Turcotte recovered

- Dr. Azad's recent publication on phage therapy for PJI (an n-of-1 clinical trial)

- Our recent Podovirus interview with Cytophage CEO Steven Theriault, whose Winnipeg-based company prepared the phages for Dr. Azad's patient, and who is partnering with her as the phage manufacturer for future cases

- Since Dr. Azad's success last year, Health Canada is beginning to enable more phage therapy: a PJI phage treatment has just taken place in Calgary by a separate group — watch the news segment here

"Phages are not drugs. Every time they say, 'Did you go through regulatory?' I say, 'I can do regulatory, but I'm not a drug.' There's 145 components of the regulatory requirements that I don't fit in."

When your health innovation doesn't fit existing regulatory boxes, how do you build a business? Steven Theriault, CEO of Cytophage, has spent 9 years learning to navigate Canada's regulatory maze for phage therapy. From being told "we don't know" by government officials to raising $24M and treating patients, Steven shares his hard-won playbook for building in uncharted regulatory territory.

In this episode of the Podovirus Podcast, Jessica Sacher and Joe Campbell talk to Steven Theriault about what he's tried, accomplished and learned in the last ~decade building a phage biotech company in Canada:

🎯 The pivot strategy: When hospitals won't buy your innovation, find another market (Steven turned to chicken farmers when Clorox contracts blocked hospital sales) 

🏛️ Educating regulators: How to teach government officials about your technology when they've never heard of it (Steven went from 10 officials with no idea what a phage was, to regular advisory calls to shape Canada's approach to regulating phage therapy)

📋 Creating your own framework: Why Steven argues phages need different GMP guidelines than traditional drugs, and how to advocate for biological variability 

💰 Funding the unfundable: How Cytophage raised $24M for technology that doesn't fit traditional pharma investment models

🔄 The workaround approach: Building revenue streams (agriculture) to fund your real mission (human health) when direct paths are blocked

🌐 International advantage: Why Steven has more regulatory traction in the US than Canada, and how to leverage global progress domestically

Learn more:

Cytophage website: https://cytophage.com/

Steven's 2024 TEDx talk on the future of phage therapy: https://www.youtube.com/watch?v=OyfbKOLNlWg

The CBC News story on Cytophage's first patient treatment: Thea's success story: https://www.cbc.ca/news/canada/manitoba/phage-therapy-infection-1.7156333

"This feels just like the early days of the HIV crisis. People are dying, you're not hearing about it. We need a group like ACT UP to bring this to the public. We're not going to get phage therapy until people start demanding we have it." 

On this episode, we talk to phage therapy patient advocate Chris Shaffer about how he fought for access to phage therapy to save his own life, and how it's led him to advocate on behalf of other patients being told there's "nothing left" for their infections. 

He draws parallels between phage advocacy and 1980s AIDS activism, while sharing his successful treatment journey to Tbilisi, Georgia for phage therapy. He shares his vision for a patient-centered future where anyone, not just the well-connected or the lucky, can access phage therapy if it could help them. 

Here's a taste of what we covered:

1. 🦠 Chris's battle with a drug-resistant infection that antibiotics couldn't cure, and how after two years of suffering, he was completely cured in just four months with phage therapy

2. 🧪 The major obstacles to phage therapy access in the US: lack of awareness among doctors, patient trust issues, and difficulty finding phages that match specific infections

3. 🏥 The striking cost difference: Chris's complete phage treatment at Eliava (including doctor visits, tests, and therapy) cost $4,600 vs. $10,000+ for just a single round of IV antibiotics in the US

4. 🔬 How the FDA actually considers phages safe enough that they don't require the same safety testing as antibiotics - but this information isn't reaching patients or doctors

5. 📢 Why Chris believes we need more vocal advocacy similar to the HIV/AIDS movement in the 1980s-90s to push for greater phage therapy access

6. 📱 Practical ideas for improving access through non-profit phage centers, better education for medical students, and targeted communication strategies

Learn more:

- Chris Shaffer's book about his phage therapy journey: https://www.amazon.com/FINDING-PHAGE-Partnered-Bacterial-Superinfection/dp/1733418296

- Chris’ website: https://phagetherapyusa.com/

- Case study on Chris’ case, published in the International Journal of Clinical Virology: https://www.clinvirologyjournal.com/articles/ijcv-aid1059.php

- Eliava Phage Therapy Center in Tbilisi, Georgia: https://eliavaphagetherapy.com/ 

- 2021 FDA-NIAID Workshop on Phage Therapy transcripts mentioned during the conversation: https://www.fda.gov/media/159401/download

- Pranav Johri's case study that helped Chris trust phage therapy: https://pubmed.ncbi.nlm.nih.gov/37790805/

- An youtube interview we did with Pranav about his story: https://www.youtube.com/watch?v=V-Qso4q52CY

- An interview we published in Capsid & Tail on Pranav's story: https://phage.directory/capsid/phage-therapy-access-india#article

- The PASTEUR Act, which Chris mentions: a bill in US congress (still has not passed) on changing how antimicrobials can be paid for by the government: https://www.contagionlive.com/view/an-update-on-the-pasteur-act

"Finally, finally we have Phase 2 data. We put a dent in the theory that phage therapy doesn't work. Maybe it does work. Maybe it's worth taking a risk."

Jonathan Solomon joins Jessica Sacher and Joe Campbell on the Podovirus Podcast to discuss BiomX's exciting Phase 2 clinical trial results, where they used bacteriophages to treat diabetic foot osteomyelitis (DFO). With 40% of DFO patients facing amputation, this is an area of massive unmet need. Jonathan shares how their trial was designed (he credits the team at Adaptive Phage Therapeutics, which began the trial prior to its merge with BiomX), and how it achieved what many of us have almost given up on: positive, statistically significant clinical efficacy data for a phage therapy treatment*.

Here's a taste of what we covered:

1. 🔬 The "Head of the Snake" theory – why many diabetic foot ID docs believe targeting Staph aureus alone works even in polymicrobial infections

2. 💉 Their phage delivery approach: combining IV "debulking" with topical phage application to help break down biofilms

3. 🏥 How 12 out of 13 phage-treated patients with bone-deep ulcers showed significant tissue rebuilding vs. only 5 of 9 in the placebo group

4. 💰 The commercial viability challenge: "If you're not seeing a 30% improvement, no one would pay for an expensive phage therapy"

5. 🧪 How personalized medicine meets practicality – the decision to use just one optimized phage per patient

6. 🔭 BiomX's dual-program approach with both DFO and cystic fibrosis trials showing promising results

Learn more!

1. BiomX Positive Phase 2 Diabetic Foot Osteomyelitis Results

2. The details of BiomX/Adaptive Phage Therapeutics’ DANCE trial

3. Recent key opinion leader discussion of Diabetic foot osteomyelitis results

4. BiomX Positive Part 2 Phase1b/2a trial of Cystic Fibrosis results

5. BiomX (NYSE: PHGE) website

*Added context

Timestamp ~22:50: Technophage (a biotech company in Portugal) did run a prior Phase 1/2a trial for diabetic foot infections. While the study showed their TP-102 phage cocktail was well tolerated and safe, and reported improved outcomes, the authors report it was underpowered to determine the superiority of TP-102 over placebo, as it ended before reaching the final target of 18 patients due to slow recruitment. Technophage is currently running a larger version of this study. 

Of note, there has been one other successful phase 2 phage trial: the Wright et al. ear infection trial published in 2009. This clinical program would have moved to phase 3, but corporate priorities shifted around the time of the ‘08 crash, and it was dropped (check out this interview with trial lead David Harper to learn more). Phage companies have been trying to re-reach this milestone ever since. Finally, it’s been reached.

"I was so biased. I knew too much and that's why we couldn't see the obvious answer that was right in front of us for years."

In this episode of the Podovirus Podcast, we explore the intersection of AI and phage biology with Professors José Penadés and Tiago Costa from Imperial College London. They share their recent discovery about phage-inducible chromosomal islands (PICIs) and how Google's new (not-yet-released) AI co-scientist tool independently reached the same conclusions they had spent years working toward—revealing how tailless phage capsids can bind with different phage tails to expand their host range.

Here's a taste of what we discussed:

1. 🧬 First, the biology: José and Tiago discovered that sometimes the end product of a viral lifecycle isn't infectious (yet). It might instead float around as a half-virus (a 'tail-less capsid'), and even mix and match with halves (tails) of other viruses floating around, enabling it to get into a vast array of totally different cells with one simple genetic code. This is the story of PICIs (phage-inducible chromosomal islands). 

2. 🤖 How Google's AI co-scientist tool—without access to their unpublished data on this project—accurately proposed the hypotheses and experiments it took them years to come up with (because they seemed to go against dogma in the field)

3. 🔬 Why 'knowing too much' can be an obstacle to discovery in science, the beauty of an unbiased companion, piecing apart what they would have done differently if they'd had AI all along, and how José and Tiago will be using AI tools going forward

Chapters

00:00 Introduction: AI + phage research, and why we wanted to talk to José and Tiago!

02:10 First, the biology background: exploring PICIs (phage-inducible chromosomal islands) and their significance

10:13 The role of AI in hypothesis generation

19:08 Interpreting data and overcoming bias

28:40 Future implications of AI in phage therapy

37:25 Experimental evidence and hypotheses validation

40:46 AI tools and their effectiveness

44:38 Interpreting AI outputs and experimental design

51:30 The role of AI in scientific discovery

57:30 Future of AI in research and collaboration

Papers discussed:

1. José and Tiago's new preprint on the science of PICIs: https://www.biorxiv.org/content/10.1101/2025.02.11.637232v1.full

2. Their companion preprint on exactly how they worked with the AI co-scientist (+ benchmarking against other AI tools!): https://www.biorxiv.org/content/10.1101/2025.02.19.639094v1 

More info about Google's AI co-scientist: https://research.google/blog/accelerating-scientific-breakthroughs-with-an-ai-co-scientist/

More info about their research: 

José's lab: https://profiles.imperial.ac.uk/j.penades/about

Tiago's lab: https://profiles.imperial.ac.uk/t.costa

Want to learn more about phage satellites? Check out this new Nature Reviews Microbiology by José's team: https://www.nature.com/articles/s41579-025-01156-z

“Getting our foot through the door to any VC... As soon as they hear we're infectious disease, their eyes kind of get big. And then they hear we're antibacterial, their eyes get bigger. And then they hear we're not small molecule, it's like all the alarm bells are ringing.”

In this episode, we sit down with Amanda Burkardt (CEO) and Mayukh Das (COO) of Phiogen Pharmaceuticals, a new entrant in the phage therapy space, to tackle one of the field's most pressing questions: can phage therapy succeed as a business where antibiotics have struggled? Drawing from their experience building a phage company from scratch, and recent discussions with Medicare, they share how they're thinking about drug pricing, reimbursement strategies, and how they’re navigating investor skepticism in antimicrobial development.

Takeaways:

- Starting with clear differentiation is crucial - Phiogen's directed evolution platform allows them to enhance desired phage properties

- The antibiotics market's poor track record has created significant barriers for phage therapy companies seeking investment

- Unforeseen post-approval monitoring costs contributed to Achaogen’s bankruptcy, and must be factored into business planning

- Recent approvals of Live Biologic Products (LBPs) for recurrent C. diff provide a potential pathway for phage therapy pricing (~$10,000 per treatment)

- CMS (Medicare/Medicaid) engagement early in development is critical for establishing reimbursement strategies — they are happy to talk to startups!

- The UK's subscription model for antimicrobials could provide significant value (~$100M over 3 years) for qualifying companies

- Phage companies must demonstrate value beyond one-time treatment to justify higher price points

- Infrastructure development, like standardized susceptibility testing, remains a critical need

- The field needs both fixed cocktails for mainstream use and flexibility for personalized approaches

- Success requires alignment between unmet medical need, pricing strategy, and reimbursement policies

Chapters:

00:00 Introduction to Phiogen and business challenges in phage therapy

08:10 Phiogen's technology platform and differentiation strategy

15:13 Navigating investor skepticism in antimicrobials

27:29 Reimbursement strategies and pricing models

35:04 Learning from Live Biologic Product approvals

43:59 The Pasteur Act and subscription models

47:27 Five and fifteen year outlook for phage therapy

Key Quotes:

“Getting our foot through the door to any VC... As soon as they hear we're infectious disease, their eyes kind of get big. And then they hear we're antibacterial, their eyes get bigger. And then they hear we're not small molecule, it's like all the alarm bells are ringing.”

"As long as people are dying and there are unmet medical needs, it is doable. Getting the business model to support that is going to be more challenging, but it is a real problem. There are people dying and there are people suffering. And so as long as that will be the case, there is a need.”

"By utilizing some high throughput methods, we could actually train phages in a way that hadn't been done before. And we're able to utilize this machine to enhance whatever antibacterial capabilities we want.”

Learn more:

- John Rex’s financial post-mortem on antibiotic company Achaogen: https://amr.solutions/2024/10/14/plazomicin-achaogen-financial-post-mortem-passpasteur/

- UK subscription model for antimicrobials: https://www.england.nhs.uk/publication/antimicrobial-products-subscription-model-guidance-on-commercial-arrangements/

- Pasteur Act information: https://www.congress.gov/bill/118th-congress/senate-bill/1355

- A blog post Amanda wrote last year for Capsid & Tail on Phiogen's approach to phage therapy: https://phage.directory/capsid/phiogen-missing-middle-ground#article: "The Missing Middle Ground of Phage Therapy: Effective Phage Therapeutics that Bridge Economy, Regulation, and Unprecedented Functionality"

"Somebody's father, friend, husband just passed away in the most developed country in the world... from a simple infection that probably could have been treated in Georgia."

In this episode, we sit down with Dr. Alexander (Sandro) Sulakvelidze to explore his journey in growing a phage therapy company from scratch, from food to human therapy. Growing up in the Republic of Georgia, phage therapy was a normal thing for Sandro; when he came to the US and saw people dying of preventable infections, he founded Intralytix. This was 26 years ago.

Takeaways:

- Starting with food safety applications proved crucial for Intralytix's survival and success as one of the few profitable phage companies

- The field has transformed from complete skepticism to active engagement, with hundreds attending phage conferences and multiple clinical trials underway

- Current regulatory concerns about transducing phages may be disproportionate given natural background levels in the human gut

- Personalized, customized phage cocktails consistently show better results than "mainstream" fixed cocktails

- Modern healthcare lacks the infrastructure for phage therapy - there's no equivalent to antibiotic susceptibility testing

- AI and machine learning are revolutionizing phage manufacturing, Intralytix is seeing 100% success in predicting optimal production conditions

- The next 5 years may see limited adoption through personalized medicine and nutraceuticals, while mainstream adoption could take 15+ years

- Phage therapy's future may extend beyond infectious disease to microbiome modulation for conditions like obesity and neurological disorders

- Proof of efficacy in rigorous clinical trials remains the critical barrier to widespread adoption and insurance coverage

- The field needs both mainstream products and the flexibility to customize treatments for individual patients

Chapters:

00:00 Introduction to Phage Therapy and Background

06:01 Evolution of Phage Therapy and Regulatory Changes

11:51 Skepticism and Acceptance of Phage Therapy in the West

20:11 Challenges in FDA Approval and Transduction Concerns

26:09 Personalized Medicine and Future of Phage Therapy

35:36 Navigating Regulatory Challenges in Phage Therapy

38:31 Research Gaps and Future Directions

41:45 Infrastructure and Logistical Hurdles

44:31 The Need for Standardization in Phage Testing

46:15 Cross-Pollination Between Food Safety and Human Health

50:38 Future Outlook: Phage Therapy in 5 to 15 Years

57:07 Challenges Ahead: Efficacy and Regulatory Concerns

Key Quotes:

"Deep in my heart, there is no doubt this works. There's just too many successful stories."

"My experience with FDA has been very good... The people we've dealt with have been reasonable."

"The variables you have to examine are mind boggling... We use artificial intelligence to learn what creates the best conditions to grow each phage."

"We are one of the very few phage companies today that actually has sales revenues... If you ignore the very long time, we're probably the only phage company that has some profit."

"The customized cocktail always worked better... scientifically and technically, it has a better chance of working."

Learn more about Intralytix: https://www.intralytix.com/

What's it like to be a doctor treating patients with phage therapy in the US today?

Dr. Gina Suh, Mayo Clinic infectious disease physician, tells us:

- How she established phage therapy as an option for her patients at Mayo

- How phages have helped her patients

- What's been hardest

- Where she's hopeful

- Where things have gotten worse

- What's next

This episode, I'm joined by my phage friend Joe Campbell (former NIH program officer)!

This is part 1 of a series we'll be co-hosting together, digging into phage therapy from multiple perspectives, trying to answer our curiosities about what's holding phage therapy back in this country and beyond — stay tuned! 

Chapters

00:00 Introduction to our new phage therapy series

01:23 Dr. Gina Suh's journey into phage therapy

06:01 How Gina has shifted how she selects patients for phage therapy

14:35 Challenges Gina has faced with phage therapy

17:46 Research needs: what the field should be studying

26:16 Infrastructure needs: Gina's wishlist

44:34 Gina's phage therapy aspirations

55:18 Why are there no support groups for antibiotic resistance?

Watch this episode on YouTube: https://youtu.be/b2NBYn4jEUo

Learn more: 

Paper by Gina and team: Considerations for the use of phage therapy in clinical practice: https://pubmed.ncbi.nlm.nih.gov/35041506/

Video: Gina Suh and John Haverty talk about John's treatment with phages (2021): https://youtu.be/XZPLt6wkh5A?si=PxSZAYmOkn2KICLs

Welcome to the Podovirus podcast, episode 3! In this episode, I talk with Jesus Fernandez-Rodriguez from Eligo Bioscience, a Paris-based biotech company pioneering microbiome editing using modified bacteriophages.

We talk about Eligo’s recent Nature publication, “In situ targeted base editing of bacteria in the mouse gut”, how it works, and what the team is thinking of doing with it.