Discussion of ASM and Phage Therapy

0:05 All right, it is a great pleasure for this episode, to talk about ASM and phage. Before we introduce our guests, I am gonna introduce Bekah Dedrick. Most of you may know Rebekah from her work at the CF Foundation and the podcast she did with me recently. But I'll let her introduce herself a little further before we introduce the guests.

0:34 Thanks, Joe. Yep, I'm a research director at the Cystic Fibrosis Foundation, where I am in charge of the academic anti-infective portfolio. I also serve as an alliance manager for some of our anti-infective industry investments. But I should say that, all views that I, talk about here on this podcast are my own, and not reflective of what the Cystic Fibrosis Foundation believes.

1:03 So thanks for having me as co-host, Joe.

1:06 Okay, great, let's start out. We have two guests from ASM today, and I'll let them introduce themselves.

1:15 Hi, my name is Dev Mittar. I am scientific director for the health unit of ASM. I'm a microbiologist by training, and most of my career has been in product development in the areas of diagnostics, health security, infectious disease, and public health. I have worked in diverse sectors, with industry and nonprofits. My last stint was in government, at BARDA, HHS, and I joined ASM about a year and a half ago.

1:50 Yep, and then my name is Neha Prasad. I was brought on to the ASM Health team about six months ago. I'm a molecular microbiologist by training. And I got into the world of phage through a collaboration with Joe Bondy-Denomy back at UCSF during my PhD. I have since held roles at BARDA, the Antimicrobials Branch, also at the Cystic Fibrosis Foundation, Felix Biotech, a couple others.

2:19 Great, so let's just start out with what lured you both into phage therapy.

2:26 Well, when I joined ASM Health, I was asked to build a strategy around where microbial sciences can make the biggest impact in human health. So I worked closely with our health chair, Colleen Kraft from Emory, and with our 14-member scientific advisory council. And by working with them, we shortlisted four major initiatives for ASM Health, which include diagnostics, multi-omics, microbiome science, and phage therapy.

2:59 So as we explored all these different areas, phage therapy kept standing out to me. Honestly, I don't consider myself a phage expert. But the more I learned about phage therapy, the more I became convinced about its scientific promise. At ASM, our central role is to convene people. And what I felt in the phage therapy field was that there are so many passionate people who are doing great work helping patients, and we clearly saw the need for convening them.

3:31 So early on, when we were discussing this, I asked this question: if phage therapy is so promising, then why are so few patients getting phage therapy in the US? So what I found in those conversations was that it is not due to the science behind phage therapy. The challenges that people are talking about were related to coordination, workflows, access, and how difficult it was to connect all the pieces together for someone to get phage therapy in the US.

4:03 So I tend to look, at the problem through a product development perspective. And the more I learned about phage therapy, the more I felt that this was one area where ASM could make a meaningful contribution. And that's how we sort of started this phage therapy initiative at ASM.

4:24 Yeah, and then for me, like I said, my start in phage was in the lab, but phage therapy kept rearing its head. Over the course of, you know, my career so far, at BARDA, you know, we were supporting a phage therapy company in clinical stages. Also, you know, worked closely with some of the CARB-X companies, some of which were developing phages. During my fellowship with the Cystic Fibrosis Foundation, I was looking into, you know, the portfolio of phage companies that they were investing in and looking at their clinical data to support whether or not, you know, they should continue with investments in those, assets specifically.

5:06 And then, you know, I entered the world of market access and reimbursement through a consulting role at Rubrum Advising. And I really wanted to learn the big picture of, you know, how do we make antimicrobial products commercially sustainable? You know, I saw this as a big problem for phage, where, you know, we were all rushing towards developing phage, and getting regulatory approval. But then what would happen once phage hit the market?

5:33 Would it suffer the same fate as antibiotics right now, where they all go bankrupt within a couple years? And so I was really fortunate to be invited by Dev to come join this group and really bring that commercial perspective into the picture early. And so that's what I'm most excited about doing here.

5:57 That's awesome, you know? I'm sure our listeners are curious, and I'm also curious, you know, why is phage therapy a priority for ASM in particular?

6:07 Well, at ASM Health, we are always looking for areas where microbial sciences can make a real difference in people's lives. As I said earlier, we are focusing on four or five major areas, which include diagnostics, multi-omics, microbiome, therapeutic innovation, and phage therapy. So our health chair, Colleen Kraft, as I said earlier, is from Emory. She is a clinician; she comes at it from the clinician side.

6:40 She takes care of patients and sees firsthand what happens when treatment starts running out. So combining her perspective with my product development background really led to this prioritization. As we talked to people in the phage field, one thing that became clear pretty quickly was that the science is very, very exciting. And as I said, there are incredible people doing great work on phage therapy. But we kept hearing about challenges across coordination and how difficult it was to navigate the system, especially for a clinician.

7:13 So that was the real moment when we thought, maybe this is where ASM can help. By the way, at ASM, we are not a phage therapy company, we are not a hospital or a regulator. Our role is to bring people together. That is what ASM has been doing for more than a hundred years. And when we looked at phage therapy, it felt like a natural place for us to contribute.

7:37 Because so much progress, depends upon connecting the right people and organizations together for this field.

7:47 Great, so I mean, you've already touched on it a little bit, but do you wanna dig a little deeper into the core problems that you hope to focus on?

7:58 When I first started learning about phage therapy, the more I talked to people, I kept coming back to a simple question. If there are so many remarkable success stories around phage therapy, why are so few patients in the US actually receiving phage therapy? So part of the answer is that we are still very, very early in the US. Most treatments today happen through compassionate or expanded access pathways.

8:29 Every case is highly individualized and requires finding the right expert, identifying a matching phage, coordinating, manufacturing, preparing regulatory documentation, and navigating hospital approvals. We invited, Steffanie Strathdee in our Microbe meeting earlier this year, and she gave an excellent talk where she described phage therapy as a global scavenger hunt, where matching the right phage to a particular infection is such a daunting task. And it currently relies on very informal networks.

9:07 There is no process. From what I learned, on average, it takes fifty three days for a patient to get the phage treatment, and in the US, it is even longer. And as you know, unfortunately, many AMR-infected patients don't have that much time, so that's the core problem ASM is focusing on.

9:30 If I could just follow up: do you have a breakdown? Do you have any idea? Is that usually the identification of the phage that matches the isolate or the manufacturing of it, or some combination of both?

9:47 All of the above. I think that is what delays it. We have published an article which says that phage therapy is like a funnel. There are multiple steps and patients, stop at, different steps.

10:04 Yeah, and I was just gonna say that, you know, I think some of that time depends on if there's a phage library available, or you're looking for new phage and how fast the organism grows, you know, from my time in Graham Hatfull's lab at the University of Pittsburgh. We were working with Mycobacterium, abscessus isolates, or sometimes MAC isolates, and those took much longer to grow.

10:27 So, of course, that time's gonna be extended depending on the biology of the specific bacteria that are causing the infection. So, yeah, I totally agree. I mean, it can be a long time, so I've heard about ASM, developing this PTCN. Can you tell us more about that and how that sort of vision for PTCN occurred?

10:53 Yeah, so PTCN stands for Phage Therapy Coordination Network, so you can think of it as a network of experts who are on this mission to improve patient access to phage therapy through coordination. So we have two types of participants. One is a core group of 16 individuals. These are physicians, regulators, manufacturers, and researchers. And they've really helped us develop the vision for PTCN and provide high-level guidance, as to what direction we're going in.

11:27 Then we have this extended network of phage therapy enthusiasts across all domains. And they have provided input through LinkedIn. We have a group that I invite everyone to join, it's through ASM Health, and we also invite, you know, members to participate in working groups. We'll talk about this a little bit later, but we've already, you know, launched one and we have an open call for another one.

11:55 But we invite, you know, everyone in this extended network to come partner with us. The vision for PTCN, and, you know, what outputs we were going to work on and what direction we wanted to go in really became clear when we convened our core group for a kickoff meeting. And we basically listened to them speak about the key bottlenecks limiting patient access to phage therapy, just from all different angles and their professional experience, what they've seen, and basically, in these conversations, we heard these experts really come to a consensus.

12:30 And, you know, come to ASM with a strong ask, you know, like, this is the missing piece. We really need a national coordination layer, and so that's really what we set out to do with PTCN.

12:43 So, besides developing that network, what were some of the big themes that sort of came out of those discussions?

12:51 So right now, I think there's this perception that, you know, there aren't so many individuals being treated with phage therapy. And I think the kickoff meeting reinforced that, you know, the way we're set up to deliver phage therapy is just nowhere near the demand that phage therapy centers are seeing from, you know, patient emails flooding their inboxes. And so, you know, they're really looking for a way to scale up, and, you know, with that scale-up, would come, you know, larger volume, more use of phage therapy.

13:22 Similar to the way we've seen around the world, how it's really exploded.

13:28 Great, so, I mean, maybe you can elaborate a little bit more on what scaling phage therapy means to you?

13:35 I think when you look around the world, you can see what greater scale starts to look like. Now there are countries like Georgia and Poland that have treated thousands of patients with phage therapy for decades, and they have built dedicated centers and clinical infrastructure around it. In the US, unfortunately, we are still largely operating one patient at a time. So what inspired me were the success stories, in those countries, patients receive treatment because clinicians, researchers, manufacturers and advocates are willing to go far beyond what would normally be expected.

14:18 So those efforts were incredibly important because they demonstrated that phage therapy is possible. But we cannot build a healthcare infrastructure around heroics around individual cases. We have to be very, very practical. So at ASM, we thought of starting something like PTCN, starting with something smaller that could eventually be scaled. So we are not ready to scale it up right now, but we have to start somewhere.

14:50 And just to add on to that, you know, if every patient needs a rescue mission, we're just never gonna reach the scale that's needed. So right now, you know, we're trying to start with US hospitals, and see if we can really grow adoption there, and so scaling phage therapy kind of means creating a system where access is more predictable. The coordination is faster, and patients don't have to depend on these extraordinary efforts that, you know, we read about in books just to find treatment.

15:22 When, you know, antibiotics are not quite doing their job, so the goal of PTCN is really then to create these systematic processes for reliably finding and delivering phage therapy through national coordination. And I think some of the metrics we talked about with the core group and internally, I think success just looks like faster time to treatment and a larger volume of phage therapy cases.

15:49 Right, so maybe if you could elaborate a little bit more. If coordination is the problem, what do you think the solution will actually look like?

15:58 We brainstormed it a lot and we came up with a solution: the Phage Therapy Coordination Platform in the United States, which is the missing infrastructure layer for national coordination. So think of it as a web platform that uses AI and automation to enable real-time collaboration among physicians, phage banks, manufacturers, regulators. That's our vision. I want to acknowledge that there are already some fantastic resources in this space.

16:34 If you look around, there are organizations like, Phage Directory, Phage Australia, Phagistry, Phage Foundries, and several other national centers. They have done a tremendous amount of work to advance the field and support both patients and clinicians. We would like to capitalize on these precedents by partnering with some of them. I must say that each of the existing resources tends to solve a specific, piece in this puzzle, with some focusing on information sharing and others on mainly phage therapy publications, some successful cases.

17:13 Honestly, most of these portals have retrospective data about phage collections, research, clinical programs, but they are static. They are not interactive, where, as a clinician, you can get all the answers. So what we really don't have today is a place where all these pieces come together in a coordinated and mostly interactive way. That's where we came up with the idea of Phage Therapy Coordination Platform.

17:41 PTCP. We all know that science exists, expertise exists, but some of the resources are already out there. What we are trying to build is a connective tissue that brings everything together. So initially, we wanna focus on the United States, but eventually we would like to expand this PTCP globally. As you said, we may sign agreements with some of the people who have access to the evidence that phage therapy works and other clinical cases.

18:14 There are manufacturing companies outside the US as well. We would like to invite them as well. So we are currently doing some fundraising and we wanna highlight the importance of evidence pieces from other countries. So those evidence pieces can be used by US clinicians to figure out a strategy for treating the patients infected with sort of similar AMR strains. So our vision is Phage Therapy Coordination Platform, and currently we are actively doing fundraising for this PTCP.

18:48 So, can you tell us a little bit about how exactly the PTCP would work?

18:55 Yeah, so the way I see it, the PTCP platform has a few major functions. So the first, you know, it starts with standardized case intake, so physicians can upload, anonymized patient cases with sequencing of the infection and a deadline. You know, when do they want the phage by? What does the phage need to be able to do? And this gets added as an open case on this like PTCP dashboard page.

19:24 Then you have this automated matching and notification part of the platform. So based on the infection genotype, we have, you know, in silico matchmaking algorithms that rank like the top ten most promising phages and notify the phage banks that they may have a potential match.

19:49 So I'm just thinking about if there's no phage match predicted, will in vitro testing be conducted?

19:58 So that's a great question for, you know, our PTCN working groups, who are really, you know, the technical experts on these types of topics. But I'm guessing, you know, we would likely default to the current practice of, you know, notifying a lab or a phage bank or a manufacturer that has a library of phage that target that particular bacterial species. You know, you had previously mentioned, you know, a specific, you know, lab that's known for producing phage against specific bacterial targets.

20:28 And so if a physician, you know, ends up seeing that same infection type, the system could potentially just alert that lab and say, we have no existing matches in our repository right now, but you might have something in your…

20:41 Yeah, yeah, that makes sense, okay?

20:46 And just to follow up, when, a match is identified, what do you envision happening next?

20:53 So next, the platform has this workflow management tool. So it's across all these different stakeholders that Dev mentioned, who need to all be connected, in almost a group chat, you know, where they all have some real-time collaboration opportunity. So this part would include, you know, step-by-step guidance: what do you do next? Templates, for example, you know, the IND, filing paperwork, different tracking, right?

21:24 What step of the process are you in, what's coming up next? And then clinical decision support tools. So how do you know, physicians know how exactly to administer the phage? What does treatment monitoring look like? All these different aspects would be coordinated through this workflow management tool.

21:45 And then, you know, I'm just curious about what you do with all of that information. So you generate data, maybe there's a match to a particular infection, maybe there isn't, or maybe a person was treated and it worked or it didn't work. What happens to that information that's generated from those cases?

22:06 Yeah, so we're being very intentional about translating all this information generated from these open cases into learnings that can inform future care. Even to address, you know, the question you asked earlier, what percentage of patients are dropping out at the different parts of the funnel? We basically want PTCP to enable standardized, real-world evidence in a centralized database. We were even imagining, like a data explorer tab, you know, that can kind of collate information across all these closed and ongoing cases, and you can kind of play around with it.

22:41 As a physician or a manufacturer, just to understand, how these cases have been progressing, what's been working, what's been tried, but with the real-world evidence that we collect as part of this, you know, national registry, we see a lot of potential here in, like, playing a role in defining a streamlined regulatory pathway for phage, potentially, you know, beyond, what's required right now in terms of standalone clinical trials for a standardized set of phage, through the BLA pathway.

23:14 So, you know, of course, this would require patients and physicians to provide consent to deposit this de-identified information. It would require, you know, a lot of collaboration with regulators here to see if we can really make this like a robust data collection arm to support that regulatory streamlining.

23:34 Great, so PTCP, seems almost like an air traffic control system for phage therapy. Can you talk about how AI fits into that picture?

23:45 So that's a good analogy, actually, an air traffic control system. And I think AI has an important role to play. And honestly, we are at a point where it is so easy to build a platform like PTCP with AI, which can bring people, data and workflows all together. So a few years ago, building something like this would have been much harder. Today we can consolidate information from multiple sources, analyze data at scale very fast, automate routine processes, and connect people much more efficiently within, like, days.

24:24 So we are certainly not shying away from the use of AI. In fact, one of the reasons I'm excited about PTCP is because we are finally reaching a point where technologies like AI can help us address some of the practical challenges in phage therapy. That's an excellent use case for AI, I guess. So take phage matchmaking, for example. Right now, finding the right phage can be incredibly time consuming.

24:51 So we worked with the company Precise Health, who has shown that with AI, phage matchmaking is possible. So José and his team are using AI and computational approaches to help predict phage-host interactions and to identify potential phage candidates much faster than the traditional approach. So I think, as more clinical, genomic and outcome data become available, AI can help us learn from every case, identify patterns, prioritize phage candidates, and make it easier for physicians to navigate.

25:30 what is becoming an increasingly complex ecosystem, but I don't see AI replacing clinicians, scientists or lab testing people here. The real challenge is still coordination, and AI is one of the tools that can help us coordinate more effectively, thereby reducing delays and ultimately helping patients to get phage therapy faster. So at the end of the day, this is still people helping patients. AI simply gives us an opportunity to do it faster and at a larger scale. I guess.

26:10 Do either of you have any idea of the percentage of clinical isolates for which a phage match can be identified based strictly on AI or DNA sequencing? And in addition to that, do you know the false-positive or false-negative rate for AI and DNA sequencing of phage identification?

26:35 Yeah, I think these are really important, parameters to keep track of. As you know, there are multiple academic and commercial groups that are really developing these genotype-based, phage matchmaking algorithms, right? And they're all trained on a different data set, you know, and all these data sets are still growing, you know, they're not at their optimal level right now, you know, so they're all kind of working differently here.

27:09 And one of the challenges we're gonna face is figuring out how to implement, you know, these algorithms within PTCP, and make sure, you know, it's working optimally. I think it's also gonna be important to leave some room, like some flexibility for in vitro testing, you know, like we mentioned, if there are no matches, or, you know, if we're finding that the matching algorithm is not great for a specific bacterial species.

27:36 Just being able to very quickly iterate on that and reconfigure the system to be able to point, physicians to the correct labs that can maybe do it in a more traditional way. But I think we're, you know, looking into the future as this is, you know, a multi-year initiative. And we're hopeful that, you know, these algorithms are only gonna get better from here.

28:01 Yeah, I'm sure they will. And then, fast-forwarding five years, can you talk a little bit about what you think success is hopefully gonna look like?

28:12 Yeah, I think five years from now, I would love to see a physician anywhere in the country know exactly where to go when they have a patient who may benefit from phage therapy. You know, and it's not just, you know, the ID docs, or, you know, these very specifically trained specialists, but, you know, even I'm thinking about surgical doctors, you know, all these other areas where phage could have utility.

28:38 And just having that awareness in the field and having a platform where people know where to go to get what they need, is really exciting. So, you know, instead of this whole scavenger hunt, like they've alluded to, you know, they would have access to these established workflows, trusted resources, and a community that's ready to help.

28:59 Honestly, five years feels like a lifetime. These days, technology is moving super fast, AI is moving faster than we imagined, and we are hopeful that phage therapy will move fast too. So I'd love to see a future where phage therapy is no longer something available only to a handful of experts who know how to navigate it. Our vision is a physician should know where to go, a patient should know where to start, right?

29:29 People should be connected quickly, and the processes should be measured in days, not months. I'd love to see us move from individual success stories to a true ecosystem where clinicians, physicians, phage centers, manufacturers, regulators, and all technology partners are connected and learning from each case. So, at the end of the day, success isn't the platform itself. Success is, I guess, getting the right treatment to the right patient faster.

30:01 And if we can help more people, then we can do it today.

30:07 Great, so do you wanna expand a little bit and say what you think is needed to get there?

30:16 I think first is expertise, and obviously, convening, that's where ASM is more comfortable. We are bringing the right people together, we wanna build consensus in developing guidance, that will help the field mature. That's what we have been doing for many years, convening people and working through working groups of experts. That is our bread and butter, and that's the first thing, we need to do to get there.

30:45 And to expand on the working groups, you know, this will be a group of experts who will create guidelines, establish standards, and compile resources that will be fed into PTCP ultimately. So they're not just standalone, you know, publications for the sake of publications, but rather something that can feed into a very practical use case. So far, we've established the clinical use guidance working group, and they'll develop, you know, clinical guidance and decision support tools.

31:14 How do you choose which patient? Treatment monitoring, et cetera. We have an open call right now for the regulatory and implementation pathways working group that will focus on simplifying hospital onboarding and IND-related processes. Basically, you know, how can we work in the regulatory framework and the, you know, the commercial landscape that we have today, where all these phage therapies are currently in clinical trials or available through expanded access.

31:43 The last two working groups are the phage matching workflow integration and finally, the manufacturing quality and CMC standards.

31:53 So I think these working groups are the foundation. Before you build technology, you need agreement on best practices, workflows, standards. That's why we are starting there. But if we are being honest, expertise alone won't get us where we want to go. If we truly want to build national coordination infrastructure for phage therapy, we need technology partners, we need funding as well. Building a platform like this, maintaining it, integrating all data sources, supporting the community takes resources.

32:30 So we are interested in working with foundations, we are working with federal agencies, philanthropies, technology companies, cloud partners, industry partners. Anyone who believes phage therapy deserves some kind of infrastructure that other areas of healthcare have built over time. So my hope is that five or ten years from now, when a physician is considering phage therapy for a patient, there should be a clear pathway. Instead of, like, a series of phone calls, personal connections, emails and whatnot.

33:04 So that's what the future looks like.

33:09 And are you all planning to work with organizations like IPATH at UC San Diego, or the Center for Innovative Phage Applications and Therapeutics, or Yale Center for Phage Biology, the Pitt phage program? There are so many of them. I wonder if you're planning on using those centers as resources.

33:29 Absolutely, organizations, like IPATH, Yale, Pitt, UCs, and they have done an incredible amount of work on phage therapy. They have treated patients, they have built expertise, some of them have developed workflows and helped push the field forward. Honestly, we are not trying to replace any of that. In fact, we wanna learn from all of them. The question we are asking is, how do we take what these pioneering centers have learned and make it easier for other hospitals and physicians to benefit from their expertise?

34:00 That's where ASM comes in. We are conveners, as I said; we bring all these people together. So if phage therapy is going to scale, it won't happen because one center, one organization does it. It is going to happen because the entire community comes together, and that's exactly the future we're trying to support at ASM.

34:21 So, sort of shifting gears a little bit. What gives you all the most optimism about the future of phage therapy?

34:30 For me, it's a couple of things. First, the people. I think being new to the field of phage therapy, it is amazing to see how phage therapy folks want to work together and are willing to help and share what they have learned. And this goes beyond the US. We routinely get emails from across the globe from phage therapy folks to participate in our working groups. I find this collaborative spirit very, very special.

35:00 And secondly, I think we are at an inflection point. When I look ten years ahead, I don't think phage therapy will look the way it does today. Right now, we are talking mostly about compassionate use cases, highly customized treatments. My hope is that we'll start seeing some more standardized approaches, including phage cocktails developed for specific infections and eventually available, much more like traditional pharmaceutical products. And I sincerely hope that big pharma will start looking at the phage therapy field sooner, and they will also start investing in it.

35:39 I know that won't happen overnight, but it feels much more achievable today than it did a few years ago. So I think the combination of better science, better data, AI, manufacturing advances, and a growing community coming together makes me genuinely optimistic about where the field is headed.

36:03 Yeah, and I think for me, yes, ten years from now is a very exciting future that they have painted. But also ten years ago, like, you know, when I was just getting started in phage and learning about it. It was all about, you know, anecdotes, it was all, you know, can phage therapy even work? You know, is this just a crazy idea, just a moonshot chance of working, you know?

36:28 And today we're discussing infrastructure to support scaling, you know, that's a sign that the field is maturing. Even as the clinical trial data for these, you know, standardized and personalized approaches are still being collected. You know, whether we're talking about engineered phage or natural phage, there are just so many different ways we're all going about it. And I think, you know, this pathway that we found at ASM to kind of take the existing framework and just build on it, scale it up, I think, is exciting to me.

37:02 Great, well, this has been a wonderful conversation and I welcome the two of you to give us any last parting thoughts before we just thank you for agreeing to have this conversation with us.

37:17 Thank you for having us. We are in a fundraising mode and we encourage everyone to support phage therapy and the platform that we are building.

37:29 We also encourage listeners to follow the ASM Health LinkedIn page I mentioned earlier. That's the best way to get involved and join the conversation. We're also hosting a webinar about PTCP. We've got featured guests who are developing, you know, technology solutions that meet some of the components of the system that we're trying to build. And this webinar will be hosted on October twenty seventh, during World Phage Week.

37:58 So we invite you to register through the ASM website. There'll be announcements posted on the LinkedIn page.

38:05 Wonderful, thank you so much. Nice to talk to you. Have a nice day.