Deploying Viruses To Counter Antibiotics Resistance With Paldara's William Colton

An increasingly common obstacle to treating patients with infections is resistance to antibiotics. In this episode of Sit and Deliver, CEO William Colton of biologics platform delivery developer Paldara Pharmaceuticals talks with videocast host Tom von Gunden about infection-combatting alternatives using hydrogel-based systems to deliver bacteriophage viral therapeutics directly to infection sites.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Sit and Deliver. My name is Tom von Gunden, Chief Editor at Drug Delivery Leader and your host for the series. Today I am joined by William Colton, who is CEO at Paldara Pharmaceuticals, which is a platform development company.

Welcome, William.

Wiliam Colton, CEO, Paldara Pharmaceuticals:

Hi. Thank you so much for having me, Tom. I really appreciate it. Yes, at Paldara, we're developing a platform drug delivery technology to help stabilize and localize delivery of sensitive biologics. So, I really appreciate the opportunity to highlight that today.

Sure. Well, it's my pleasure to have you here. Thanks for joining.

So, let's start where I like to start, and that is in the patient landscape. So, what's front-of-mind for you out there in terms of scenarios and conditions in the patient world that you're focusing on approaches to?

Yes, so the main kind of crisis we're addressing is the antibiotic resistance crisis. And that's been a growing issue over the past 20, 30 years. As we know, the advent of antibiotics started with penicillin, and antibiotics have been a wonder drug for the healthcare system. It makes it extremely easy to treat these really risky infections and manage them.

But the problem is now [that] resistance has become prevalent throughout the healthcare system, and even more so in hospital systems as selective pressure is highest there. That's where antibiotics are used most commonly.

And so, these pathogens have evolved resistance to multiple mechanisms of antibiotics, and we're running out of therapeutic options in clinical settings to treat them — so much so that now 1 in 10 patients will die from antibiotic resistant infection in our current healthcare system. So, this is a huge impact, and it disproportionately affects the elderly, the young, and immunocompromised — so, the most vulnerable in our population. These infections usually happen underneath hospital care, and these patients are at high risk.

And so, with these drug-resistant infections, therapeutics a lot of times are even more toxic than some of the infections. So, using antibiotics, like colistin, these are last-line antibiotics with high toxicity. And so, patient outcomes are not great. We're trying to enable a new stage of technology, bacteriophage-based therapeutics — small viruses that actually prey upon these bacteria and can overcome this resistance. Our technology enables them to be easier to use in those kinds of clinical settings to help with those patient outcomes.

Great. Could you tell us a little bit more about that science and technology? Take a little bit deeper dive into just exactly what it is that you're developing or creating and how it moves and what it does.

So, to touch more on the technology we're enabling: So, bacteriophage therapeutics: bacteriophages are small, naturally occurring viruses that only infect bacteria. They're not pathogenic to humans; they're part of our microbiome. They occur all around us; they're part of our natural microenvironment, and they regulate bacterial populations. Their main goal is to help control these bacterial populations and prevent them from becoming too over-populous and disrupting the microbiome.

We're able to harness that to be able to attack and treat directly these specific drug-resistant infections by completely circumventing antibiotics and using these viruses to target and eliminate the bacteria. And again, well-tolerated, well-experienced by the body. We just need new therapeutics to make them easier to use in healthcare settings as the viruses alone are pretty sensitive.

So. our hydrogel drug delivery technology helps to give them a stable microenvironment for extended periods of time at room temperature for a wide range of different viruses. So, we can enable the next generation of phage therapeutics to be easier to use in a gel kind of format for these clinicians, something that's familiar to them.

Gotcha. And so, is there a range of routes of administration through which this approach can be delivered?

Yes, we have to modify the formulation slightly, but we have a flexible breadth of applications. So, we've looked at topical applications for a hydrogel. There are enteric delivery methods by modifying the formulation where we can treat infections like C. diff, which are extremely problematic and cause antibiotic use. We've looked at dry powder inhalation formulations for indications like tuberculosis and multi-drug-resistant TB.

And then we've looked at joint infections. So, hydrogels that are able to be put inside the body that prevent scar tissue formation, support wound care and healing, while also fighting off and preventing active infection from forming.

So, there's a wide application of different formulations we can implement by just tweaking this hydrogel cocktail we work with.

Great. And so, if you could illustrate that from the patient perspective in terms of receiving a treatment: Pick any scenario or indication that you'd like. What might a common experience be like for a patient receiving a treatment in this way?

Yes, so personally for me, I lost my grandmother to a joint replacement infection. She fell when she was in a nursing home, broke her hip, and ended up needing a hip replacement. And what happened was, that hip replacement — that metal implant — became contaminated and infected with drug-resistant staph. And so, they ran out of antibiotic options, put her on a central line, which is intravenous infusion of antibiotics, which they knew would not work, but could try and slow down the growth of the bacteria. And upped her morphine over a period of six months until she went septic and passed.

What could have been implemented with our kind of technology is, during that procedure when they're introducing that foreign implant, a thin hydrogel coating can be applied by the physician at the time of implantation around where the excision site is, where that implant is being placed, around the surrounding tissue. And the hydrogel is biocompatible, would help support wound care, support the healing process, prevent fibrotic tissue formation, but also slowly release the phage at the site of care.

What we're trying to do is prevent bacterial invasion during these really complex procedures from getting to the point where it has contaminated the implant. And now it's the body versus the implant, which is kind of neutral territory for these bacteria to propagate, form biofilm, and put the patient's life at risk. So, by simply adding that one step in, we could have saved a patient like my grandmother.

Yeah, yeah. Well, it sounds, of course, much needed and promising. So, as the work continues there, the folks at Paldara, including you, obviously: As the development continues on its way, hopefully, to eventual commercialization, what's the model? How do you fit into the ecosystem, or might? I understand, for example, that you already have a partnership with the Mayo Clinic for development purposes.

Yeah, so there's a lot of interest from the healthcare organization sector from the clinical standpoint because these hospital-acquired infections pose a huge risk for these hospital facilities and their management corporations. They're having to pay out-of-pocket to take care of these patients, and it puts their hospital at risk if they have too many of these infections going on within their healthcare system.

And remember, they've run out of options. We don't have antibiotics to treat these infections anymore. So, they're desperate for alternatives that are effective while still being able to address these potential outbreaks [that] are taking place across healthcare systems in the U.S.

And so, being able to have these options that function both as a prophylaxis, preventing the spread of these infections, but also a therapeutic, being able to treat these active infections, gives them a double-edged sword that works against two key major negative impacts that essentially cut out the bottom line in a lot of healthcare systems and pose a lot of risks to their patients. So, we're taking that worry out of the healthcare system.

Excellent, excellent. Well, I like to end with a look out onto the horizon, whether that's near or far (you can tell us where you think that might be): As you look out there at the future state of patient health and lives — should these advancements move forward and take hold as we anticipate and hope that they will — what do you envision that future state for patients to look like?

I envision a future where patients aren't having to worry about these drug-resistant infections. Where someone with cystic fibrosis and having to go in and worry about, hey, am I going to get diagnosed with another drug-resistant infection because I have a preexisting condition and I'm susceptible, and now I'm going to have to fight off something else and take these antibiotics that make me feel sick every day?

And we can provide them with an alternative, which is a gel powder that they can inhale to treat their drug-resistant, pseudomonas infection and help manage that without the toxic side effects. And these phages are really effective with their job. They've evolved to do this. It's their sole, niche purpose.

So being able to enable those therapeutics for those patients means less doctor visits, better patient outcomes, and better security and less pain for these patients on a large scale. And if we can just help one, like the doctors we've worked with have, it's worth it all. So that's the main goal.

Yeah, well, I can certainly hear the passion and commitment coming through in the way you described that, and especially in the way you shared your personal experience and story with it.

So, I want to thank you, William, for joining today for this episode of Sit and Deliver and sharing your perspectives on the work being done there at Paldara Pharmaceuticals. And to our audience, I want to thank you for joining for another episode, and we'll see you next time.