Peptilogics: Using AI-Powered Peptides to Combat Prosthetic Joint Infections

Funding announcements in biotech are more than business headlines—they're signals of scientific momentum and bets on new ways of understanding or treating disease.

These moments offer a glimpse into where science is headed, what investors are prioritizing, and how novel biology is making its way toward the clinic.

In this series, we're covering early-stage biotech companies that recently raised capital, spotlighting the ideas—and the science—behind them. Next up: Peptilogics.

Peptilogics' Bold Goal: Eliminate Biofilm-Protected Infections

Peptilogics, a Pittsburgh-based clinical-stage biotechnology company, is tackling one of orthopedic surgery's most devastating complications: prosthetic joint infections (PJI). The company combines artificial intelligence and peptide therapeutics to address infections that current antibiotics cannot eliminate.

It's an ambitious effort aimed at a serious and growing condition. With 45,000 PJI cases annually in the U.S. and no approved therapeutics specifically indicated for this condition, patients face limited and often unsuccessful treatment options.

Why PJI Needs New Approaches

Prosthetic joint infections are a devastating complication that can turn a successful joint replacement into a patient's worst nightmare. Despite multiple surgeries and extended courses of high-dose antibiotics, treatment fails up to 50% of the time, requiring additional and even more aggressive interventions, including surgical removal of the infected joint.

The toll is high: a 25% five-year mortality rate—worse than many cancers—and treatment costs that can exceed $150,000 per procedure. With the average patient requiring 2-3 surgeries, total costs often exceed $390,000 per patient.

At the molecular level, the challenge lies in biofilm. "Hardware-related infections are difficult to treat because bacteria on foreign surfaces hide in these dense, drug-resistant layers that shield pathogens from current antibiotics," says Nick Pachuda, a former orthopedic surgeon and Peptilogics Chief Operating Officer.

That leaves a significant gap in care—and a clear opportunity for better solutions.

AI-Powered Peptide Platform: The Nautilus Advantage

Peptilogics is taking a novel approach by integrating artificial intelligence into peptide drug discovery through its proprietary Nautilus AI platform. The platform combines deep generative models, predictive models, and biophysical simulation to design multiparameter-optimized peptides that address historically challenging drug targets.

"We start by focusing on the principles that guide biology," says founder and CEO Jonathan Steckbeck, PhD. "If we can learn and understand how systems operate at a fundamental level, we can build algorithms that predict how new molecules will behave—and we can do it with speed."

The company's engineered cationic antibiotic peptide (eCAP) platform generated zaloganan (PLG0206), its lead clinical candidate. Zaloganan was designed with a unique mechanism of action that allows it to directly address persistent bacterial pathogens within biofilm by targeting and disrupting bacterial membranes to trigger bacterial cell death.

Peptides—short chains of amino acids—offer a balance between the strengths of biologics and small molecules. They are highly specific with activity against major drug-resistant pathogens and can penetrate biofilm that conventional antibiotics cannot.

"Zaloganan quickly penetrates the biofilm locally and kills the hiding bacteria," explains Pachuda.

Leadership & Expertise

Peptilogics is led by a team of experienced professionals in drug discovery, computational biology, and clinical development:

Jonathan Steckbeck, PhD, MBA, Founder and CEO: Steckbeck founded Peptilogics in 2013 following personal loss that inspired his commitment to developing novel therapeutics for life-threatening infections.

Nicholas Nystrom, PhD, Chief Technology Officer: Oversees the Nautilus AI platform and its integration of proprietary deep generative models with supercomputing capabilities.

Nick Pachuda, Chief Operating Officer: A former orthopedic surgeon who brings clinical expertise and insight into the challenges facing PJI patients.

The company benefits from Pittsburgh's robust biotech ecosystem, which has supported its growth from inception through clinical-stage development.

Funding & Backing

Peptilogics recently announced the completion of an oversubscribed $78 million Series B2 financing round in October 2025. Presight Capital, Thiel Bio, and Founders Fund led the round, with participation from new investors AMR Action Fund, Narya Capital, and Beyond Ventures.

Combined with the company's previous $35.4 million Series B financing in 2020 led by Presight Capital and Founders Fund, this brings Peptilogics' total disclosed equity funding to approximately $113 million, along with substantial grant support from CARB-X. The financing will enable Peptilogics to advance zaloganan into Phase 2/3 pivotal trials.

This substantial funding round highlights growing investor interest in antimicrobial resistance solutions and surgical therapeutics.

Clinical Progress & Milestones

Zaloganan has demonstrated remarkable clinical promise. In Peptilogics' Phase 1b study, zaloganan irrigation administered during DAIR (debridement, antibiotics, and implant retention) procedures resulted in 13 of 14 patients (93%) remaining infection-free at 12 months.

These encouraging results compare favorably against historical DAIR failure rates of approximately 50% in published literature. The company has set ambitious goals for advancing zaloganan through pivotal trials:

• December 2025: Phase 2/3 randomized, placebo-controlled superiority trial begins enrollment of 240 patients.
• Primary endpoint: Measuring reduction in clinical failure rates.
• Secondary measures: Health economics including hospitalization duration, readmission rates, and additional surgical procedures to quantify cost savings.

In both in vitro and non-clinical studies, zaloganan has demonstrated best-in-class, rapidly bactericidal, broad-spectrum activity against pathogens identified by the World Health Organization and Centers for Disease Control and Prevention as critical, urgent, or high-priority targets, regardless of resistance phenotype.

Regulatory Advantages

Peptilogics has received multiple regulatory designations that support the development pathway for zaloganan:

• QIDP (Qualified Infectious Disease Product) designation: Provides 5 additional years of market exclusivity upon approval.
• Orphan Drug Designation: For the treatment of PJI.
• Fast Track Designation: To facilitate development and expedite FDA review.

Zaloganan has the potential to be the first approved therapy specifically indicated for the treatment of periprosthetic joint infection.

Market Opportunity & Competitive Edge

The challenge is growing as more joint replacement surgeries are expected. Projections show that by 2030, 3.48 million knee and 572,000 hip replacements will be performed annually in the U.S., each carrying PJI risk.

"What these investors understood is that hardware-related infections like PJI are different from other common infections," said CEO Steckbeck. "We chose to focus on this huge unmet need because the lack of effective therapeutic options alters the commercial landscape that has made antibiotic development difficult."

Peptilogics' AI-powered approach offers distinct competitive advantages. The Nautilus platform enables efficient navigation of the vast peptide design space, allowing the company to uncover molecules that may not be discovered through traditional screening. This combination of proprietary AI algorithms, supercomputing capabilities, and biological expertise positions Peptilogics to address antimicrobial resistance challenges at unprecedented speed and scale.

Looking Ahead

Peptilogics is positioned to create a new category of surgical therapeutics for patients who currently have to undergo multiple life-changing surgeries to eliminate infections. By combining significant capital, top-tier talent, and proprietary AI-driven peptide design technologies, the company holds credible potential to deliver the first approved treatment specifically for prosthetic joint infections.

"Periprosthetic joint infections are a striking example of how antimicrobial resistance is rapidly undermining modern medicine," said AMR Action Fund CEO Henry Skinner, PhD. "The financial costs, diminished quality of life, and mortality associated with such infections are frankly unacceptable, and we are pleased to support the Peptilogics team as they advance zaloganan through the clinic and toward patients in need."

The company's success in Phase 1b trials and substantial investor backing signal strong momentum as zaloganan advances into pivotal studies. For patients facing devastating prosthetic joint infections, Peptilogics' AI-powered approach represents hope for a future where biofilm-protected bacteria no longer dictate treatment outcomes.