Leyden Labs reports first human data for intranasal flu prevention antibody

The update covers two phase 1 trials in which a total of 143 healthy volunteers received intranasal doses of Leyden’s lead antibody candidate. The studies focused on safety and tolerability and showed that the antibody could be administered locally to the nasal cavity and detected there following dosing. However, no clinical endpoints related to protection or antiviral activity were reported in humans.

Alongside the human data, Leyden highlighted preclinical and non-human primate studies in which intranasal administration of the antibody was associated with reduced infection or viral replication. Those animal results are the basis of the efficacy discussion in the announcement.

This update comes a year after Leyden Labs announced a $70 million financing round in January 2025 to advance its mucosal antibody platform and initiate human efficacy studies of its PanFlu nasal spray candidate.

A long-standing antibody with a new delivery strategy

The antibody at the centre of Leyden Labs’ influenza program, CR9114, is not a newly discovered molecule. It is a broadly neutralising anti-influenza monoclonal antibody first described more than a decade ago in a study to identify targets less vulnerable to seasonal viral drift.

CR9114 was originally reported in 2012 as part of research led by investigators at Scripps Research Institute and Crucell, then a subsidiary of Johnson & Johnson. At the time, most neutralising influenza antibodies were known to bind the highly variable head region of hemagglutinin (HA), limiting their activity to closely related strains. CR9114 stood out because it bound a conserved epitope in the HA stem, a region involved in the membrane fusion process and far less tolerant to mutation. The study showed that this allowed broad activity across multiple influenza A subtypes, as well as influenza B.

The discovery was framed at the time as a proof point for the feasibility of universal flu antibodies, but translating such molecules into practical prevention strategies proved more difficult. Systemically delivered antibodies face challenges around dosing, durability and cost, particularly for large, seasonal populations.

Leyden Labs’ contribution isn’t the antibody itself, but how it is used. The company holds an exclusive licence from Janssen to develop CR9114 as an intranasal product, steering away from systemic exposure to local delivery at the nasal mucosa, where influenza infection typically begins. The idea is that concentrating antibodies at the site of viral entry could reduce the doses required for prevention.

Where existing flu prevention falls short

Seasonal influenza prevention still relies mainly on vaccination, but performance varies by season and population, and protection is often weaker in older adults. That variability is one reason the field keeps returning to broad biological approaches, including monoclonal antibodies that bind conserved regions of hemagglutinin, as a potential complement to vaccines.

Systemic anti-influenza antibodies have been explored in the clinic with mixed results. Visterra’s VIS410, for example, was reported as safe and associated with favourable effects on symptom resolution and viral replication in adults with uncomplicated influenza A, but it did not establish a straightforward route to mass, seasonal prevention. Genentech’s MHAA4549A, meanwhile, did not improve clinical outcomes when added to standard-of-care oseltamivir in hospitalised influenza A patients and did not further reduce viral load. Even when antibodies look broadly active on paper, systemic delivery ties prevention to high doses, logistics, and cost at a seasonal scale.

This is the variable Leyden wants to address with its intranasal strategy. The company is trying to concentrate antibodies in the nasal cavity, to maximise local exposure while keeping the total dose low. Now that we know Leyden Labs’ candidate is safe for humans, the next question will be about its efficacy.