ENA respiratory launches phase 2 community study of INNA-051 nasal spray

ENA Respiratory has announced a key milestone in the clinical development of INNA-051, an investigational nasal spray designed to bolster the body’s natural antiviral defenses and reduce the burden of common respiratory viral infections.

The company noted that its Phase 2 community study, known as POSITS, has started with the first participants being dosed in January. The aim of the study is to evaluate the safety, tolerability and potential effectiveness of the therapy in preventing symptomatic respiratory infections.

“This study is an important next step for ENA Respiratory and for the development of INNA-051,” said Christophe Demaison, Ph.D., CEO of ENA Respiratory.

He highlighted the urgent need for broad-spectrum preventive tools amid continued high levels of viral respiratory illness, particularly among vulnerable populations such as older adults and people with underlying conditions like asthma, chronic obstructive pulmonary disease, cardiovascular disease, diabetes and cancer.

INNA-051 represents a novel approach to respiratory viral disease prevention. Unlike vaccines or direct-acting antiviral drugs that target specific pathogens, the therapy is a once-weekly dry powder nasal spray that activates innate immune pathways in the nasal mucosa, where infections with respiratory viruses such as influenza, RSV, rhinovirus and coronaviruses initially begin.

Its mechanism harnesses a small molecule agonist of toll-like receptors 2 and 6 (TLR2/6), receptors that play a central role in recognizing pathogens and stimulating the body’s first line of defense.

According to Demaison, the Phase 2 trial is designed to assess both the safety and activity of INNA-051 across a broader, community-based population. It will include an initial safety cohort of about 200 participants receiving weekly doses for four weeks during the ongoing North American respiratory virus season, followed by a larger Phase B cohort of up to 900 participants who could be dosed for three months.

Those being targeted for the study include people considered at high risk for exposure due to living or working in crowded settings such as university housing, barracks and households with young children.

Demaison noted hospitalizations and deaths tied to respiratory viruses remain substantial, underscoring the potential public health impact of an effective prophylactic such as INNA-051.

“The politics and economics of respiratory disease prevention have evolved significantly,” he said. “Seasonal respiratory viruses are a perennial burden, driving hospitalizations, straining health systems, and causing millions of missed workdays and school absences each year. Efforts to control these infections have traditionally relied on pathogen-specific vaccines such as seasonal flu shots and reactive antiviral treatments. However, there has long been an unmet need for approaches that provide broad, virus-agnostic protection, particularly one that can be easily administered in community settings and adopted widely.”

An early Phase 1 trial and a Phase 2a influenza challenge study suggested that INNA-051 is well-tolerated and capable of activating local innate immune responses that can accelerate viral clearance. Those studies also indicated that boosting local antiviral defenses may reduce the duration and severity of respiratory symptoms when exposed to viruses like influenza in controlled settings.

The POSITS Phase 2 study will be one of the largest community-based trials of an innate immune prime for respiratory disease, enrolling up to 1,100 generally healthy adults aged 18 to 45 who are at increased risk of exposure. Conducting the study during the fall and winter respiratory season in North America provides a high-incidence environment in which to observe potential effects.

Demaison noted the Phase 2 data will be critical in determining whether the promise seen in earlier trials translates into real-world impact, especially among populations at elevated risk of complications.

ENA Respiratory has positioned INNA-051 as a weekly, easy-to-use prophylactic option, which is a contrast to daily medications or seasonally targeted vaccines, with the potential for room-temperature storage and broad public health application if proven safe and effective.