As antibiotic resistance erodes the power of our oldest drugs, entrepreneur–researcher William Colton and his company Paldara Pharmaceuticals are betting on a far older ally: bacteriophages—viruses that prey on bacteria. Paldara has developed a hydrogel delivery platform that stabilizes phages without cold-chain logistics and releases them precisely at the infection site, helping them evade immune neutralization and act where they’re needed most. Through the Mayo–ASU MedTech Accelerator, Paldara forged a know-how and sponsored-research collaboration with Mayo Clinic physicians to translate the platform to cases like prosthetic joint and surgical-site infections. In this Q&A, Colton explains how phage therapeutics differ from antibiotics, where Paldara fits into the global AMR fight, and the personal story driving his mission.
Not everyone knows what bacteriophage therapy entails—or even what phages are. Can you introduce that first?
Absolutely. Almost all living things have viruses that infect them—think of humans with the flu or COVID. Similarly, bacteria have their own viruses, called bacteriophages, and they’re part of every kind of micro-ecosystem. Even in our microbiome, bacteriophages naturally live inside us and help regulate bacterial populations. Phages are viruses for bacteria. They’re very different from the viruses that infect our own cells because they’re adapted to bacteria; they don’t affect our cells or our bodies. They’ve existed essentially since the advent of single-celled organisms and persist today. Given that antibiotics developed 50–100 years ago are already becoming obsolete, why not use this natural control mechanism as a therapeutic? We’re harnessing evolutionary power for modern medicine.
How does phage therapy potentially address the antibiotic-resistance problem we have?
When you think of a traditional antibiotic, it’s essentially a poison that targets something conserved in bacteria but not in humans, so it’s not toxic to us. For example, penicillin—a beta-lactam antibiotic—targets structures in bacteria that differ from ours. The issue is that when you target a conserved trait, it can take just one mutation for the drug to stop working. With phage therapeutics, once phages infect a bacterial cell, they don’t rely on a single target site—they hijack the entire cell and turn it into a factory for new phages. Antibiotics don’t self-replicate; phages do. It can take just one phage encountering its target bacterium to start a whole treatment cascade. And each new generation can adapt to the bacteria. Antibiotics don’t do that. When our therapeutics can’t adapt, resistance develops rapidly.
Let’s get to your hydrogel platform. How does it work, and what makes it particularly suited for delivering bacteriophage therapeutics?
The technology is based on hydrogels—essentially a mesh of polymers, repeating chains of polysaccharides. Think pectin in fruit jelly: it’s a polysaccharide matrix that gels in water. We take that web of polysaccharides and, via lyophilization (freeze-drying), pull out the water so the mesh shrinks around the phages along with small stabilizing sugars—almost like bubble wrap. The freeze-dried hydrogel condenses around the phage and protects it. Our hydrogel has two key components: (1) microencapsulation, which further protects the phage and lets us co-deliver other therapeutics, and (2) a time-release matrix that controls phage release after application. You can think of the hydrogel as the “Intel chip” for phage therapeutics—making them much more functional in real-world settings and helping with bench-to-bedside translation.
If I’m understanding correctly, your hydrogel addresses a longstanding issue in phage therapy—how the host immune system reacts to introduced phages.
Yes. Traditionally, many phage therapies are delivered intravenously, dumping phages into the bloodstream, which can be problematic. By using a hydrogel, we localize the therapeutic at the site of care rather than systemically. That reduces inflammation, immune responses, off-target effects, and neutralization. The hydrogel also acts as a physical barrier against neutralizing antibodies and phagocytic cells (like macrophages) that might destroy phages before they work. It’s integral to making promising phage therapeutics actually work in a human clinical setting.
The hydrogel also eliminates a lot of cold-chain requirements. How transformative is that for deployment in resource-limited environments?
It’s huge. Phage therapeutics are self-amplifying and relatively easy to manufacture in large quantities compared with some molecular antibiotics. Stabilizing phages so they’re ready to use in emergencies—especially in the Global South and other low-resource areas—matters because many places lack cold-chain storage and other infrastructure. Providing a low-cost, stable therapeutic that’s ready when needed can meaningfully improve quality of life globally.
Before we get to your Mayo Clinic partnership, a basics question: how do you find and select your phages?
We use clinical isolates that represent the infections we’re targeting. Take surgical-site infections and drug-resistant staph, for example. We gather ~100 clinical isolates reflecting those infections across the U.S. or another target region. We then isolate and amplify phages from environmental and microbial samples against those isolates, and screen the amplified phages against the ~100 isolates to build an optimized cocktail. Our specialty is drug delivery for next-generation antimicrobials, but using this approach lets us consider broad isolate diversity and build overlapping coverage—reducing the chance of resistance and allowing both treatment and prophylaxis.
Now onto your partnership: how did the collaboration with the Mayo Clinic come about, and what does the know-how/license agreement entail in practical terms?
We engaged with Mayo via the Mayo–ASU MedTech Accelerator and were selected as one of the top eight innovative biotech startups internationally. Through that, we connected with Mayo resources and Dr. Gina Song and her team, who were excited about a novel drug-delivery mechanism to advance phage therapeutics. After eight months of due diligence and the accelerator—where our cohort won its competition—we developed a know-how agreement and a sponsored research agreement with Dr. Song and her collaborator, Dr. Robin Battelle, at Mayo Clinic in Rochester. Over roughly two and a half years, we built a relationship that gives us access to clinical expertise, trial design input, and feedback—truly invaluable. Dr. Song is one of the few physicians in the U.S. who has repeatedly used phage therapeutics successfully to treat otherwise fatal multidrug-resistant infections. I’m not a physician; I can’t prescribe or treat patients. She’s the one saving lives. We’re incredibly grateful to work with her.
What specific infections or clinical settings will you focus on initially?
We’re finalizing that, but we’re looking at orthopedic infections—especially prosthetic joint infections—surgical-site infections, and other hospital-acquired infections. The emphasis is on vulnerable populations with significant morbidity and mortality. Mayo’s primary interest is prosthetic joint infections, and we’re exploring expansion into drug-resistant staph and soft-tissue infections. Because our approach is a platform, there’s room to grow.
Looking forward, what are the potential hurdles to broader phage-therapy adoption?
Frankly, we’re in a scientific funding crisis. Cuts to NIH support have a chilling effect on biotech innovation. Companies tackling global problems that historically received federal backing are losing the foundation that sustains high-risk, high-impact work. Navigating that landscape while prioritizing patient outcomes is the biggest hurdle.
Addressing antimicrobial resistance is a global effort. Where does Polderas’s platform fit? Are you aiming to complement existing therapies, replace them, or something else?
We see ourselves as a gateway to a new generation of antimicrobial biologics. As a stabilization and delivery platform, we enable countries—especially those with limited resources—to keep sensitive biologics on hand without cold-chain storage. For phage therapeutics, that means stockpiles for prevention and treatment of outbreaks like typhoid or tuberculosis. There’s strategic value in having “ready-to-deploy” phage rather than growing therapeutics ad hoc. We’ve begun discussions with several countries and medical experts to align on needs and tune our technology for implementation in challenging environments.
You’ve spoken about your grandmother’s tragic experience as a major motivator. How has that shaped your mission and company culture?
It’s deeply personal. I felt helpless watching her run out of options. You can’t take something straight from a lab and use it—it needs FDA pathways, efficacy testing, or emergency use authorization, which can still take too long. For my grandmother, I learned how crushing it is at the bedside when there are no options. She had a central line of vancomycin for six months and was still septic. All we could do was give her morphine. That’s no quality of life—more a slow degradation than a single moment of loss. I don’t want anyone else to go through that. If I can contribute to giving people hope and an alternative to what my grandmother endured, that’s what drives me.
It’s a tribute to your grandmother.
Thank you. And it’s not just her—this is happening all the time. It’s a serious, ongoing problem.
I’m sure Polderas will succeed and play a real role in improving quality of life.
That’s the goal. Progress that tangibly helps people.