Silent Shield: Nasal Spray Enters Trials to Block Respiratory Viruses

By Frank Reed

MELBOURNE, Australia – January 29, 2026 – In the ongoing battle against seasonal colds, flu, and other respiratory threats, a novel approach is gaining ground. Australian-based ENA Respiratory announced today it has dosed the first participants in a major Phase II clinical trial for INNA-051, a once-weekly nasal spray designed not to treat, but to prevent symptomatic viral infections before they take hold.

The study, dubbed ‘POSITS’, marks a critical step forward for a technology that could shift the paradigm from reactive treatment to proactive, broad-spectrum defense. The virus-agnostic dry powder spray aims to prime the body’s innate immune system in the nasal passages—the primary entry point for pathogens like influenza, RSV, and coronaviruses—offering a new layer of protection for millions.

A New Paradigm in Prophylaxis

Unlike traditional vaccines that train the immune system to recognize a specific virus, INNA-051 works by enhancing the body's own first line of defense. It is a potent agonist of Toll-like receptor 2/6 (TLR2/6), a key protein in the innate immune system that acts as a sentinel, recognizing pathogens and triggering an immediate, localized antiviral response.

By activating these receptors in the nasal mucosa, the spray essentially puts the immune system on high alert. This pre-emptive priming enables the body to respond more quickly and effectively when it encounters an actual virus, potentially clearing the pathogen before it can cause symptoms, replicate, and spread to the lungs. This “virus-agnostic” mechanism is a key differentiator; it doesn't matter if the threat is a familiar flu strain or a novel coronavirus, the boosted innate response is designed to be universally effective.

This approach positions INNA-051 as a powerful complement to existing public health tools. While vaccines remain crucial, they are often strain-specific and can take weeks to become fully effective. Direct-acting antivirals like Tamiflu or Paxlovid are treatments that must be taken shortly after symptoms appear. INNA-051, with its convenient once-weekly prophylactic dosing, aims to fill the gap, offering sustained, broad protection, particularly during peak respiratory virus seasons.

Previous studies have already shown promise. A Phase IIa human influenza-challenge study demonstrated that INNA-051 accelerated viral clearance and stimulated antiviral defenses. The localized delivery via a nasal spray is also a significant advantage, as it is designed to maximize the immune response at the site of infection while minimizing the risk of systemic side effects that have challenged other immune-boosting therapies.

The 'POSITS' Study: Targeting High-Risk Environments

The ‘POSITS’ study, officially registered as NCT07222670, is a large-scale, randomized, and placebo-controlled trial designed to rigorously test the real-world efficacy of INNA-051. The study will enroll up to 1,100 healthy adults between 18 and 45 years of age who are at increased risk of exposure due to their living or working conditions.

The trial is divided into two parts. An initial safety phase with 200 participants is now underway during the current North American respiratory season, involving weekly dosing for four weeks. This will be followed by a larger 900-participant efficacy phase next season, where individuals will use the spray for three months.

The study's primary goals are to assess the safety of the spray and its ability to reduce the incidence, duration, and severity of symptomatic respiratory infections. Researchers will be monitoring for a wide range of common viruses, including influenza, RSV, rhinovirus, and coronaviruses.

Recruitment is strategically focused on environments known to be hotbeds for viral transmission. This includes individuals in crowded households, university students in dormitories, military personnel living in barracks, and childcare workers. The first participants have already been dosed at the University of Maryland's Center for Vaccine Development and Global Health, with additional recruitment at the Naval Medical Research Command Clinical Trials Center in Maryland.

The Broader Context and Competitive Landscape

The need for new preventative tools is underscored by staggering public health data. According to ENA Respiratory, respiratory-related viral infections were responsible for over a million hospitalizations and up to 200,000 deaths in the U.S. in 2025 alone. These illnesses disproportionately affect vulnerable populations, including the elderly and those with underlying conditions like asthma, COPD, and heart disease.

“The start of the POSITS study is an important next step for ENA Respiratory and for the development of INNA-051,” said ENA Respiratory’s CEO, Christophe Demaison, PhD, in a statement. “Our previous pre-clinical and clinical work has shown INNA-051 to have the potential to shorten the duration of symptomatic infections, prevent progression to the lungs, and reduce complications... By boosting the body’s natural host defense pathways INNA-051 could offer a new option for millions of vulnerable patients worldwide.”

While other companies are exploring broad-spectrum antivirals, ENA's approach stands out. Many are focused on direct-acting drugs that inhibit viral replication, while others exploring immune modulators have faced challenges with systemic administration. INNA-051’s localized nasal delivery and specific TLR2/6 target offer a potentially safer and more targeted prophylactic profile.

Backing a Potential Game-Changer

The significant potential of INNA-051 has attracted a roster of high-profile investors and strategic partners, signaling strong confidence from both the financial and global health communities. ENA Respiratory is backed by life science venture firms like Brandon Capital and Stoic Venture Capital, as well as mission-driven organizations including Flu Lab and the Bill & Melinda Gates Foundation. The involvement of the Gates Foundation, in particular, highlights the therapy's potential for substantial global health impact.

Furthermore, the company has forged key strategic alliances. It is an alumni member of BLUE KNIGHT™, a joint initiative between Johnson & Johnson Innovation and the U.S. government's Biomedical Advanced Research and Development Authority (BARDA), which aims to accelerate solutions for future pandemic threats. This places INNA-051 squarely in the conversation around national health security and pandemic preparedness.

A partnership with the US COPD Foundation also underscores a commitment to developing the product for one of the most vulnerable patient populations. If the ‘POSITS’ trial proves successful, the data will provide a strong foundation for future studies in at-risk groups where preventing a common cold could mean preventing a life-threatening hospital stay.

As the trial gets underway, the medical and public health communities will be watching closely. Success in this Phase II study could validate innate immunity enhancement as a major pillar of respiratory health, potentially providing a simple, weekly nasal spray to serve as a silent shield for people everywhere.