FDA Aligns with Tonix on Phase 2 Study Design for TNX-4800 to Prevent Lyme Disease

Tonix Pharmaceuticals announced that it has received the official meeting minutes from a Type C meeting with the US Food and Drug Administration, confirming alignment on key aspects of its planned adaptive Phase 2 field study of TNX-4800, an investigational human monoclonal antibody targeting outer surface protein A (OspA) to prevent Lyme disease in adults.

A Type C meeting is a formal FDA interaction that provides regulatory guidance on product development. According to the company, the agency’s feedback supports initiation of the Phase 2 study in the first quarter of 2027, pending final protocol review.

TNX-4800 is a long-acting, Fc-modified anti-OspA monoclonal antibody designed to provide passive immunity against Lyme disease. Unlike vaccines that stimulate the body’s immune response, TNX-4800 is intended to provide protection within two days of administration by targeting OspA, a protein expressed on Borrelia burgdorferi while the bacteria reside in the midgut of infected deer ticks.

By targeting the bacteria before they migrate to the tick’s salivary glands, the therapy is designed to block transmission to humans. The antibody has an extended half-life and is expected to provide seasonal protection with two subcutaneous doses administered approximately three months apart. The planned study has not yet been listed on ClinicalTrials.gov.

Adaptive Phase 2 study to enroll approximately 3,300 participants

The adaptive Phase 2 study will be a randomized, placebo-controlled field trial enrolling approximately 3,300 adults over two Lyme disease seasons. Participants aged 18 years and older who live in Lyme-endemic regions of the United States and have frequent exposure to deer ticks will be randomized 1:1 to receive TNX-4800 450 mg or placebo, followed by a second dose about three months later.

The primary efficacy endpoint will evaluate prevention of Lyme disease through six months after the first dose, while a key secondary endpoint will assess protection during the first three months. Safety and tolerability will be monitored for 52 weeks. Tonix expects manufacturing to be completed for delivery to study sites during the first quarter of 2027, with most participants enrolled during the 2028 Lyme disease season, although enrollment could extend into 2029 if disease incidence is lower than anticipated.

Passive immunization strategy targets bacteria inside the tick

TNX-4800 is designed to interrupt Lyme disease transmission before infection occurs. During a tick bite, the antibody enters the tick through the blood meal and binds to OspA on B. burgdorferi, preventing bacterial maturation and migration from the tick’s midgut to its salivary glands, thereby blocking transmission to humans.

According to Tonix, previously published animal studies showed that serum concentrations of at least 21 μg/mL provided approximately 95% protection against infection in a non-human primate model following exposure to infected ticks. Because TNX-4800 provides passive immunity rather than stimulating antibody production, protection is expected to begin rapidly, making it a potential option for individuals requiring immediate seasonal protection.

Potential alternative to Lyme disease vaccination

Lyme disease is the most common vector-borne disease in the United States, with approximately 87 million people living, working, or traveling in endemic regions. Delayed diagnosis or treatment can lead to complications affecting the joints, heart, and nervous system, while some patients may develop Post-Treatment Lyme Disease Syndrome (PTLDS), characterized by persistent symptoms after recommended antibiotic treatment.

According to Tonix, there are currently no FDA-approved vaccines or monoclonal antibody therapies for the prevention of Lyme disease. If successfully developed, TNX-4800 could provide a differentiated seasonal prevention strategy through passive immunization and address an important unmet public health need.

Following FDA alignment on the proposed study design, Tonix plans to finalize the Phase 2 protocol, complete manufacturing, and initiate the adaptive field study during the first quarter of 2027, subject to regulatory and operational readiness.

Reference

Tonix Pharmaceuticals Announces Positive Minutes from Type C FDA Meeting to Discuss Adaptive Phase 2 Field Study of TNX-4800, a Human, anti-OspA Monoclonal Antibody, to Prevent Lyme Disease in the U.S.