Emerging Oral Lyme Disease Prevention Strategy and TP-05’s Potential Impact on Public Health

As Lyme disease cases continue to rise across the United States, infection prevention strategies are evolving beyond traditional behavioral measures. In this Q&A, Infection Control Today^® (ICT^®) speaks with Roxana Francisco, MD, PhD, senior director of clinical development for Tarsus Pharmaceuticals, about an investigational oral therapy that could reshape prevention by targeting ticks before transmission occurs.

ICT: From an infection prevention standpoint, how significant is the potential of an oral, on-demand therapy like TP-05 in reducing Lyme disease risk compared with current prevention strategies?

Roxana Francisco, MD, PhD: Lyme disease is the most common vector-borne disease in the U.S., with more than 30 million people at moderate to high risk and an estimated 300,000–400,000 cases diagnosed annually. Despite this, prevention today relies largely on behavioral measures—such as protective clothing, repellents, and tick checks—which can be inconsistent and often ineffective in real-world settings, particularly given the difficulty of spotting and distinguishing small ticks.

There are currently no FDA-approved pharmacological prophylactic options for Lyme disease. TP-05 is designed as an investigational oral, on-demand approach that potentially targets the root cause of infection by killing ticks before disease transmission occurs. In a previous Phase 2a trial, a single dose demonstrated statistically significant tick mortality versus placebo, supporting further development in the ongoing Phase 2 Calliope trial.

ICT: If TP-05 proves effective, how might this change public health and infection prevention messaging around tick-borne disease prevention?

RF: Current public health messaging around Lyme disease prevention focuses on avoiding tick exposure, using personal protection (repellants and clothing), and acting quickly after potential contact (body checks and prompt removal of ticks), which again, can be tricky given that ticks can be small and hard to spot.

An effective oral prophylactic option could meaningfully expand that paradigm by introducing a preventive layer that does not rely solely on behavior or early detection.

TP-05 is an investigational on-demand, seasonal approach tailored for real-world risk—potentially serving outdoor workers, military personnel, travelers, and those in endemic areas. By targeting the tick itself, it could address a critical gap in prevention and aims to stop infection before it begins.

ICT: What are the potential advantages and limitations of targeting ticks before transmission rather than focusing solely on human vaccination or post-exposure treatment?

RF: We are encouraged to see increased innovation and investment in Lyme disease from multiple players in the biopharma industry. Continued progress in prevention has the potential to make a meaningful difference for individuals and communities at risk.

Preventing Lyme disease by stopping ticks before they can transmit disease offers several advantages over post-exposure treatment. It reduces reliance on early diagnosis, which can be challenging due to missed tick bites and nonspecific early symptoms, and helps avoid the need for antibiotic treatment and the risk of debilitating, long-term complications associated with untreated disease, including persistent fatigue, joint and muscle pain, and cognitive difficulties.

TP-05 is the only nonvaccine, oral, on-demand therapeutic in development that could potentially provide flexible protection for individuals when they anticipate a higher risk of exposure, including travel to an endemic area or participation in other professional or personal outdoor activities. Furthermore, our potential nonimmunogenic approach may offer practical advantages by avoiding injectable administration and the need to induce durable/long-lasting immune responses over extended periods, which in some cases may be associated with immune‑mediated adverse effects and may be less acceptable to certain individuals.

ICT: With Lyme risk expanding due to climate change, how could a therapy like TP-05 fit into broader prevention strategies for high-risk populations and regions?

RF: As climate change drives ticks into new geographic areas, including regions historically considered low risk, the burden of tick-borne illnesses such as Lyme disease continues to grow. For high-risk populations, on-demand therapy may offer a practical way to enhance protection during periods of elevated exposure.

ICT: What considerations should infection prevention professionals keep in mind when evaluating emerging preventive therapies like TP-05 for real-world use?

RF: Lyme disease is an evolving public health challenge, underscoring the need for increased awareness, prevention strategies, and continued innovation.

If successful, TP-05 could potentially offer a first-in-class, on-demand approach to preventing Lyme disease (and potentially, other tick-borne illnesses) by targeting the source of transmission: the tick.