Leyden Labs advances RIG-101 after Phase I shows safety and on-target immune activation

Phase I data from Netherlands-based Leyden Laboratories B.V.'s intranasal innate immune modulator RIG-101 showed acceptable safety and on-target pharmacodynamic activity in both healthy volunteers and asthma patients, clearing the path to a Phase I/II rhinovirus challenge study, the company reported.

RIG-101 is a stem-loop RNA (SLR) therapeutic that agonizes RIG-I, a cytosolic innate immune receptor that, when activated, triggers type I and type III interferon production in the respiratory epithelium. The rationale for targeting asthma is epidemiological: respiratory viruses, predominantly rhinovirus, are reported to trigger more than 80% of severe asthma exacerbations. Patients with asthma are thought to have impaired baseline interferon responses, making them disproportionately vulnerable to viral-driven disease flares. RIG-101 is delivered intranasally using the proprietary NEED (Nano-Emulsion Effective Delivery) platform, a non-lipid nanoparticle system designed to deposit therapeutic payloads directly at the respiratory mucosa.

In the completed Phase I study, intranasal RIG-101 was well tolerated at all dose levels tested with up to seven days of daily administration. Biomarker analyses in asthma patients confirmed the expected pharmacodynamic signature: induction of type I and type III interferons and upregulation of interferon-stimulating genes in the upper respiratory tract. Leyden Labs described the biomarker profile as consistent with the intended mechanism of action. No quantitative efficacy or detailed safety data were disclosed.

The next planned study is the RIG 101 Trial in Healthy Adults and Adults With Asthma, a two-part, randomized, double-blind, placebo-controlled Phase I/II design. Part A covers repeat-dose safety in healthy participants and asthma patients; Part B is a human rhinovirus challenge study in asthma patients, assessing whether pre-treatment with RIG-101 reduces viral replication or clinical consequences following controlled RV-A16 inoculation. The trial is currently recruiting.

Leyden Labs acquired RIG-101 through its purchase of RIGImmune, Inc. earlier in 2026, adding the SLR therapeutic class and the NEED delivery platform to a pipeline otherwise centered on broadly protective intranasal antibodies targeting influenza, coronavirus, and rhinovirus. RIGImmune, now a Leyden Labs subsidiary, holds an exclusive license from Yale University to develop and commercialize RIG-101. The acquisition extends Leyden Labs' mucosal protection strategy beyond passive antibody-mediated neutralization into active innate immune priming — an approach that, the company argues, does not require a functional adaptive immune response and could therefore be applicable to immunocompromised patients.

Pfizer licensed RIG-I small molecule agonist technology from Kineta for oncology in 2018, and TransCode Therapeutics has published preclinical data on a separate RIG-I immunotherapeutic candidate in cancer. RIG-101's focus on respiratory protection in asthma, using an RNA-based intranasal approach, is mechanistically distinct from those oncology programs. No approved RIG-I agonist currently exists in any indication.

The rhinovirus challenge model used in Part B is a well-established methodology for generating controlled proof-of-concept efficacy data and informing subsequent respiratory drug development. A positive result there would provide evidence that pre-treatment with RIG-101 translates pharmacodynamic activity into clinical protection.

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