Defeating Superbugs 🦠 An Evolutionary Battle (Part 1)

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Hey everyone, and welcome back to the TechLink Health Podcast. I am Justine Reese, and I am co-hosting this episode with Dr. Rodney Samaan. As many reflect on the past couple of years of the pandemic and start to think about emerging threats of the future, it is important to bring awareness to that very topic. Right, the future and what's on the horizon in public health. Today's episode focuses on the emerging threat of antimicrobial resistance, which has been deemed by the World Health Organization as one of the 10 global public health threats facing humanity. During the episode, we will discuss the cutting-edge technologies that can help tackle this challenge. This episode's guest My guest is Rob McBride, co-founder and CEO of Felix Biotechnology, a technology focused on accelerating the deployment of novel biotherapeutics targeting urgent microbial challenges in health and beyond. The Felix mission is founded on creating an evolutionary solution to the evolutionary problem of microbial resistance. Rob has a PhD in ecology and evolutionary biology from the University of Houston and a Bachelor of Science from St. Vincent University. Prior to founding Felix, Rob was the co-founder of Boost Biomes, which used the powerful social networks among microbes to provide novel, sustainable solutions to feed and heal people everywhere. It goes without saying that Rob has a passion for biotechnology and innovating in the space, and we look forward to getting his perspective. So without further delay, we are really excited to welcome Rob to the podcast. Rob, thank you so much for joining us today.

Thanks so much for having me. I'm really excited to be here.

Awesome. So to start us off and give our listeners some background, can you take a moment yourself to introduce yourself in a bit more detail and tell us about your journey into the targeted biotherapeutic space?

Uh, absolutely. So my name is Rob, as you've mentioned. I have a technical background in evolutionary microbiology. And I've been in startups now for around 12 years. The theme of the activities that I've been working on is figuring out how we can leverage the enormous power that resides in microbes to create things that add value to humanity and to our future. I started off working on biofuels, then using microbes to make alternative sources of food. And then at Boost, we were using microbes to protect the agriculture in the field and protect produce on the shelf. And then I had an opportunity to team back up with a professor that was my principal investigator when I was at Yale doing a postdoc, Paul Turner, to revisit whether or not the timing was good to see if we could deploy phage as a tool to help manage bacterial infections, particularly those that are resistant to small molecules. And after thinking about the problems and looking at the toolsets that we had available to us, we felt like this was a good time and a good opportunity to really, you know, add our efforts to the rest of the folks that are trying so hard to create these new therapies and prevent a future in which many more people will die from infections than we think need to.

Absolutely. And you did give me a quick little explanation on the name Felix, and I would love for our listeners to hear that because it was pretty fascinating.

So Felix is named after Félix d'Hérelle, a scientist who was the first scientist to therapeutically deploy phage. And he did this back in 1919. So phage as a technology has been around for an extraordinarily long time. And so we decided to name the company after him. He also spent some time at Yale as a professor. And additionally, an added benefit of the name is that it also means lucky. I think its derivative is luck.

Fantastic. Well, thanks for sharing that.

So actually, I think there's a lot of history of where, if you look back at medical history, where companies Or ideas just fall to the wayside and people forget about them. This seems like one of them. Can you tell us a little bit more about that history and why it was not adopted? Was it related to sort of pharmaceutical companies wanting drugs instead of something like a virus to treat a bacterial infection? And also, I'd like to hear more about other companies. I heard about one in San Diego. that's working on this. I heard about a patient who actually got treated, last resort, for compassionate use, and they were in the ICU for many months and were treated successfully for their bacterial infection with a phage. And I'd love to hear more about that.

Yeah, great question. So let me start with a little bit of an overview of the history of phage therapy and its use. And so, we don't have to go back that far to sort of arrive at a time in which bacterial infections were similar, you know, when you got a bacterial infection, you kind of played a little bit of Russian roulette, right? So, at the was pre-1930s, we didn't really have any good tools to manage bacterial infections. So if you got a bacterial infection that, you know, was not well managed by your immune response, you had a good chance of dying. And there was a lot of effort and time put into figuring out what tools we could deploy to manage these bacterial infections. And there's a lot of fascinating history about the companies and the sort of the race to develop these new tools around that time. And so, you know, phage, people knew about it. We didn't have the tools or the technology to understand phage in a way that would allow us to harness their potential effectively, right? And so, while people were thinking about trying to generalize phage and turn them into a sort of a generalizable tool, you know, antibiotics came onto the scene. And after the end of World War II, antibiotics became more widespread, and they were, you know, very easy to use because they were broad spectrum. And so, at least in the West, the majority of interest in phage fell by the wayside as this new tool came onto the scene that, you know, seemed to be a panacea for bacterial infections. And certainly, for the duration of my life, I've I've grown up not really thinking about or being concerned about bacterial infections, and I've been fortunate enough to have received antibiotics a number of times, and, you know, they've worked. And so, fast forward to maybe 20 years ago, we started to appreciate that the broad nature of antibiotics, which has initially made us attracted to them, was also not a good thing because we have a lot of microbes that are doing good things for us. And when we take a broad-spectrum antimicrobial, we do kill the bad bacteria, but we also kill all the bacteria that are doing good things for us. And so there is this increased desire to have a more targeted therapy that can just focus on killing the bad bacteria and preserve all the benefits of the bacteria that aren't bad by not killing them. And then at, in a similar time period, we started to notice that many of the antibiotics, and this had been noticed for a while before then, but it became more apparent in the last 20 or so years, that many of the antibiotics that we did have were becoming less effective because the bacteria that they were being deployed against had developed ways to become resistant to those small molecules. And so Resistance is rising. The number of new antibiotics being developed is declining. And so we're in a situation now where if new tools and new therapies are not developed, by the year 2050, more than 10 million people a year will die from these infections. And, you know, today we're losing about 1.2 million people a year from these infections. And these are infections that are theoretically treatable, right? So if the antibiotics worked, these people would not be dying. And if we can develop tools in the future, we won't be losing the population of New York City, you know, 10 million people on an annual basis. And so that gives you a little bit of scope about how we got to this place today where, you know, there's a renewed interest in more targeted approach to managing bacterial infections. And then just talking about the space, right? So there are a number of other companies in the space who are doing great work. And I think the key thing to keep in mind is that all of us are taking slightly different approaches to how we think about deploying phage to manage bacterial infections. And Felix's approach is really focused on trying to develop phage in a way that is analogous to how we use small molecules. So we're trying to make phage as useful as possible for a specific therapeutic indication. So we need to be able to overcome what has limited phage traditionally, that is the narrowness of their host range. And so we've developed a very exciting machine learning approach to understanding what the genetic components of phage host range are, and how we can use the engineering tools that we've developed to manipulate the host range of the phage. And then we also have a very novel approach to overcome or account for the evolutionary challenges of bacterial resistance. So lots of other companies, everyone's taking a slightly different flavor. The Felix flavor is focused on generalizable phage therapies. And I do want to give a shout out to Stephanie Stratvey, whose husband was treated by phage down in San Diego. Some of the folks at Yale were actually involved in that, and it was a great example of how phage can be used in a personalized context to really save somebody's life, right?

Yeah.

And we've got a lot of examples of How phage are more and more being used in these contexts. And so that's fantastic for the people who have access and the resources to get that therapy. And what we'd like to do is capture those benefits and make them available to as many people as possible by making them generalizable.

Great.

Yeah, I think she wrote a book about it, if I'm not mistaken.

She did. The Perfect Predator. And I would encourage you all to read it if you have a chance. And Stephanie has been a great advocate for the space.

Wonderful. That's really exciting. And so, you know, I'm not sure if this is a Bill Gates moment, but many have noted that he warned about a global pandemic and we've just experienced one, but that was a viral infection and not a bacterial infection. And so, first of all, I would want to know more about why the World Health Organization has picked microbial resistance as one of the top 10 global public health threats facing humanity. And what are the implications? Why is this timing right for Felix? And also one more question to that. So this is only for bacterial, not viral infections?

That's correct. So we are developing, we are engineering viruses that are explicitly focused on killing bacteria, right? So they're very targeted to bacterial infections. And so we're taking advantage of this predator-prey interaction that has existed for millennia, and we're harnessing that interaction to our benefit, right? So these are viruses that kill bacteria, and so we're very focused just on bacterial infections. And, but, you know, as we noted in recent pandemic with COVID You know, viral infections are a huge component of infectious disease, right? So bacterial infections, viral infections, and fungal infections, these are all sort of encompassed by the generic term infectious disease. And, you know, one of the things that amazed me about the COVID pandemic was how the power of the mRNA vaccine platform to develop tools in record time to help us to, as a community, as a world, attack and really sort of nip something in the bud that could have been hugely more impactful. And so we like to think analogously that the platform that we are developing at Felix, similar to the mRNA technology that was deployed to have a huge impact on mitigating the potential detriment caused by the COVID pandemic, we can have a similar impact on this new pandemic that is growing, which is the pandemic of bacteria that kill people that are not responding to traditional tools that we use to manage them. Which are antibiotics. So your second question was with regards to why this is a big issue. And I think bottom line is there isn't really anything that you do in a hospital, right? I'm just going to use this as an example where you aren't interacting with microbes in a way where they could potentially harm you, right? So, you know, if you go in and you get tooth surgery or you get your knee fixed or you get eye surgery, you know, hospitals are continuously worried about bacteria getting into you that can cause issues, right? Especially when they're in the wrong environment. And so, you know, antibiotics are used prophylactically. get used post-surgically. And so if those tools don't work, everything that we do potentially becomes life-threatening, right? And again, just to give you a number, my understanding is that if you get a staph infection, a staph blood infection that is not resolved by your immune response, right? You don't have any tools to manage it, right? 7 out of 10 people with that infection will die, right? That's terrifying, right? And you can get this from cutting your finger in the kitchen, right? And so, If you project out into the future, the impact of not having tools to manage these infections, as I mentioned earlier, that number is around 10 million people a year by 2050. And I think no one on the planet would contest that is a future that we are not interested in, and we should all be focused, or some folks should be focused on trying to develop solutions to mitigate that from happening.

Definitely. I had to look up the word phage and the photos and the drawings, and the definition is one that devours. And I just kept thinking about Stranger Things. I don't know if— I don't want to be spoilered, but those images are really kind of scary, honestly, to look at. So it's really interesting to look at this as the virus that kills the bacteria. As someone coming into this more layman terms, it's pretty fascinating stuff. In the past on the podcast, we've covered topics related to precision medicine and personalized medicine. So with that in mind, what are some of the other potential applications for Felix Biotech? And also tell us more about programmable therapies and what are the parallels to general longevity using programmable therapies?

Uh, so lots of great questions in there. Just to touch on your commentary with regards to us using something potentially scary, like a virus, to create a beneficial health outcome. That's definitely something we're aware of, the optics of that. And it's important for us to continuously message that not all viruses are bad, right? We've grown up with this mindset that viruses are negative. Viruses that only infect bacteria, that cannot infect humans, in fact, can be our friend, right? So the enemy of my enemy is my friend. And so that's the way we think about these viruses. They are very positive for human health if they can be harnessed in the right way. So we're very excited about the potential here. And to your point about how we can use this technology more broadly, It is precision medicine, right? So we are going in and very surgically removing a subset of bacteria that is causing harm. And typically, again, if you can do that well, then you can preserve all bacteria that do good. And so, you know, having the ability to target phage specifically to bad bacteria and not to good bacteria is critical. And that's one of the benefits of the platform that we have is that it enables us to do that with precision. And it's one of the key benefits of our approach. You know, there are a number of bacterial challenges that we face. And as a company, as a small startup company, the way we think about what to go after now and what to go after in the future is determined not just by the threat posed by the bacteria, but we also want to focus initially on bacterial threats that do not have good alternative solutions, right? And that have the potential to be interesting from an investment perspective, right? So we've got a number of constraints around how we pick. bacterial targets. So I think one of the number one bacterial threats globally is tuberculosis. And, you know, we are very excited and interested about the potential of phage to manage tuberculosis, but from a deployment perspective in the US, that's not an economically viable target for us to go after initially. So for us, the targets we're focused on are bacteria that are in the lungs of patients who have cystic fibrosis. These are patients who struggle with lung infections and who take antibiotics on extended bases and in whom there is a large fraction of the bacterial population that are resistant to the tools. So the tools that they traditionally would use, inhaled antibiotics, they don't work so well anymore, right? And so we want to help those folks initially, right? And so that's where we're starting. So we're targeting bacteria like Pseudomonas aeruginosa. We're also targeting bacteria like Staphylococcus, also known as, you know, MRSA. We're focused on bacteria like NTM, nontuberculosis mycobacterium. And so these are some of the challenges that we are focused on. And again, you know, trying to think about the constraints that govern us as a small company in the US, trying to make sure that we develop returns for our investors and also help patients at the same time.

And was there any relativity to the respiratory infections that were coming, starting as COVID, that you could utilize any of these therapies that were maybe relatable?

Absolutely. I think that a huge component of mortality associated with COVID was not the virus itself, but the secondary infections that came along with the viral infection. And so having the ability to deploy a therapy that treated bacteria that wouldn't respond to small molecules or antibiotics, I think it's a great use case and a great example of the value of this type of technology. And we're extraordinarily appreciative of folks like the government, right? The NSF and the NIH for investing in technology like ours and helping us to get to the point where we can show people that the sort of the general value in a safe and effective way and hopefully get to these patients more quickly. So we weren't able to treat anybody during the COVID pandemic, but we hope that by the time the next pandemic rolls around, we'll be well positioned to help as many people as possible.

Well, on that note, you know, it's very apparent that Felix Biotech is tackling an evolutionary savvy adversary. So what are some of the other threats that we should start thinking about? Okay, so maybe the top 3, give us the top 3 threats from your point of view, Rob.

Yeah, so I'm not qualified to tell you what those are in terms of impact across the globe. It's not something we think about every day, but I would say, you know, as a small company, if you're developing a solution to manage a bacteria and you are not accounting for the fact that the bacteria is going to evolve, right? It's not when it will evolve, it is going to evolve, that you're developing a solution that is going to, by definition, have a short shelf life. And so we are very focused. Many of us come from an evolutionary background, and so we think about how to deploy phage in a way that will allow us to account for the evolution the bacteria will have towards our phage. And so one of the things we use is we design phages that will bind to receptors on the bacteria, and those receptors allow the bacteria to be dangerous, allow the bacteria to be virulent, right? And so, for example, some bacteria are able to resist antibiotics because they have a pump that has the ability to pump the antibiotics out of the bacteria. So we will design viruses that bind to that pump Right? And so the bacteria, if it wants to evolve to become resistant to the virus, it can do so by changing the pump so that the virus cannot no longer recognize the bacteria. But when the bacteria changes the pump, it also then loses the ability to get antibiotics out of the bacteria, and that bacteria becomes resensitized to antibiotics. And so this is an example of how we can take an evolutionary idea and utilize it to design a therapy that will benefit the patient more effectively in the short and the long run.

But in that case, would that be a joint therapy with antibiotics, or it would just be the phage would take care of the bacteria?

So our focus right now is just on phage itself, but the patients that we are treating are receiving other therapies at the same time. So they are receiving antibiotics, despite the fact that they don't work that well. We are very excited about the possibility of deploying simultaneously, right, as a singular therapy, phage and antibiotics. We think there are a lot of advantages to doing this, including the advantage of having increased exclusivity on a novel product and the benefits that would accrue to the patients from having the synergy of the small molecule and the virus being deployed at the same time. Well, you know, and so why we're interested in that, we're not, that's not our sort of lead asset right now.

Got it. In some of our past episodes with Technically Health, we like to think creatively on how we can help bring emerging technologies to consumers, healthcare practitioners, and organizations. And we're just wondering when and how Felix can enter our day-to-day lives.

So that's a great question, and it's wonderful that you are thinking about that. Our motto is patients can't wait. And so we're very focused on trying to get our technology as quickly as possible within the constraints of safety and efficacy to patients. And so, you know, we are very excited about and happy to talk to physicians who have exhausted all conventional options and are interested in helping us apply for compassionate use exemptions. This will allow us to get to patients who have run out of time. We are looking for folks who are passionate about this problem and would be interested in investing in this problem to help us in the longer term. So we do have a lead asset that we have licensed from Yale that is currently in an investigator-initiated trial. We are designing the commercial version of the trial. As you know, trial design is not cheap, and so we need as much sort of help as we can to make sure that we can do that well and get this into the hands of patients more generally and more broadly as quickly as possible. So I would say if you are a physician and you have a patient who does not responding to any antibiotics and you're interested in understanding more about or exploring whether or not we can help you with phage to help save that patient's life, let us know. And if you or anybody knows folks who are passionate about the space but are more interested from an investment perspective, we'd also be very interested in chatting.

Excellent. And to that note, so are the studies ongoing right now? Are they phase 1?

Yeah, so it's phase 1/2, but it's an investigator-initiated trial, right? So the outcome of that is not a sort of a filing, right? So it's not a BLA.

Sure, sure. And just one more question related to that. In terms of the compassionate use, I actually considered that for a patient with COVID As you know, many drugs were coming out or being used, and I got sort of roadblocked, number one, by hospitals, and number two, the paperwork was insane. And so I'd love for you to just talk briefly about compassionate use and that process with the FDA and how that works.

Yeah.

So I think the best case scenario is where there's good synergy between the physician, the company, the FDA, and the infrastructure that's being used to administer things to that patient, right? And so the success cases that we've had are primarily deployed by our co-founders and collaborators at Yale, working with physicians at Yale, working with the approval of the FDA and the sort of the administrators of the infrastructure there, right? And so the actual application to the FDA, there's not a ton of paperwork, keeping in mind that this is something that is on a presumably a tight time constraint. I think the FDA is very thoughtful about and considerate of trying to help patients who don't have any other options. And so they've streamlined that paperwork. I think, you know, some of the challenges come in with regards to payers reimbursing for this type of work. We're not interested in this being sort of a profit generation for us. It's just about helping patients. This isn't something that is generating revenue for us. We're just focused on doing that at cost. And so if there is openness to exploring solutions, I think that there's, it's a very real path and it's being used. I would say maybe in the hundreds of times now in the US across different institutions with the help of different companies.

And can you speak to those 100 patients that have gotten your phage therapy?

So let me be very clear. I'm sure the number of patients in the US now that have received phage on a compassionate use basis is in the hundreds. Those aren't all from Felix or from the assets that are licensed to Felix, right? We've got a case study coming out in the next month or two that'll talk about 10 patients that have received the asset that we have a license to. There's some amazing work coming out of Pittsburgh, out of Graham Hatfull and his group there have done some, you know, recent papers talking about the success they've had treating patients who have really recalcitrant bacterial infections. I know that the folks down at San Diego have done a great job. There's some folks out of Baylor in Texas that have done some great work, the Taylor Labs. So, you know, I think everybody is motivated to help patients while trying to figure out more generalizable and more sustainable solutions with the understanding that there are people who just don't have the time for this to go through the traditional FDA-approved regulatory process. And, you know, the FDA has figured out a way to help those patients, you know, if the right boxes are checked.

Got it.

And I was just curious, I know on the website it shows maybe a patient getting a shot. Is that how you administer this therapy or is it sometimes an IV? I'm sorry, I asked the layman question.

No, no, it's a great question. It really depends on where the infection is, and our goal is to get the solution to the infection site in the sort of most direct and effective way. And so currently our focus is on infections in the lungs. And so we do use what's called nebulization. So the phage is nebulized and the patients inhale that nebulization, that nebulized liquid. And so that the bacteriophage will go directly into the lungs and interact with the bacteria in the lungs.

Yeah, I intentionally, when I moved, did not throw away my nebulizer because of COVID And I did pull it out once with some saline. It's a good thing to have around, it seems like.

But you can also put phage in skin cream. People have used it on skin cream. People have given it intravenously. There's lots of different ways to apply phage. And I would say that, you know, it really depends on what you're trying to do, right?

So.

Do you think that will become more of a household word at a certain point that people are somewhat unfamiliar with right now?

I would hope so, right? It seems to me that more and more we appreciate that generalized solutions, for example, if you're putting a cream on that's killing good bacteria and bad bacteria, that's not ideal for your skin, right? Why not put a cream on that just kills bad bacteria? And also, at the same time, it's chemical-free, environmentally friendly, so on and so forth. And so, I think that as consumers become more educated about the benefits of the good bacteria that they have, as they start to deploy personal care products on their bodies, they, you know, hopefully will become more eager to deploy personal care products that are targeted, right? That will just kill bad bacteria and preserve the good bacteria, be that, you know, armpit microbiome, skin microbiome, you know, oral microbiome, et cetera, et cetera.

And to that point, I really like that point, Rob. I think you alluded to it at the beginning as well, that we're sort of taking a shotgun approach with antimicrobials. And so it's refreshing to hear a different perspective on this that hopefully will keep the microbiome in its natural state for the most part. So that's very exciting.

Yeah. So in closing, any final thoughts, advice for those that want to continue to learn more? About the AMR threat and some of the other things we've talked about and mentioned here, and also the best way to stay connected to your work, Rob, and updates with Felix.

So yeah, thank you for the opportunity to have me on. Thank you for the great questions. I definitely appreciate it. Always excited to talk about what we're passionate about and the work that keeps us engaged and working hard. I would definitely say that our website has a news site on it, which we regularly post things, including blogs and press releases. Our Twitter feed is really active. We have an amazing group of folks focused on trying to educate and help and sort of bring more eyes to the space and to the challenges that exist in the space and to the successes that happen in the space and to the amazing researchers that are working in the space. And our LinkedIn likely has, you know, in a similar fashion, has some great resources there. So those are some places I would go to. But I would just encourage everybody out there, if you're passionate about something and you're really interested in finding solutions, find companies like Velix who are working on challenges. It's not a simple thing to do, and the more folks that get on board with helping, I think the faster we all can, you know, get to a point where we can help patients. And again, this isn't just about Felix. There is a lot of amazing phage companies in the space and a lot of amazing other companies developing other solutions in the space, but we do need that because we've all grown up taking bacteria for granted, and I think that we cannot continue to do that in the future. And if we do want a future that we can be excited about, we have to figure out New tools, and we're excited at Felix to be one of the companies trying to do that.

Awesome.

Excellent. And one more question, Rob. I don't know if you can talk about this, but are you guys planning to go public?

That's a great question. We're not planning on doing that in the short term. I think the question for us is we want to get to patients as quickly as possible. And right now going public is probably not the best way. I don't know that we could go public, but it's probably not the right way for us to do that right now.

Got it.

Right.

Makes sense.

Well, good luck to you guys. We'll be cheering you on. Good luck.

Much appreciated. And thank you for taking the time. It was great chatting with both of you.

Yeah.

Great talking to you, Rob.

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