Leyden Labs Advances Intranasal RIG-I Agonist RIG-101 to Rhinovirus Challenge Trial After Phase I Safety and Biomarker Success
核心洞察
Intranasal RIG-101 was well tolerated at all tested doses in healthy volunteers and asthma (搜索) patients, including up to seven days of daily dosing.
Biomarker analyses in asthma (搜索) patients confirmed induction of type I and type III interferons and interferon-stimulated genes, matching the intended mechanism.
A two-part, randomized, placebo-controlled Phase I/II trial targeting 82 participants at two UK sites is now recruiting, with Part B testing rhinovirus (搜索) RV-A16 challenge.
Netherlands-based Leyden Laboratories (搜索) B.V. reported that its intranasal innate immune modulator RIG-101 showed acceptable safety and on-target pharmacodynamic activity in both healthy volunteers and asthma (搜索) patients in a completed Phase I study, clearing the path to a Phase I/II human rhinovirus (搜索) challenge trial. The company said RIG-101 was well tolerated at all dose levels tested, including after daily intranasal administration for up to seven days.
RIG-101 is a stem-loop RNA (SLR) therapeutic that agonizes RIG-I (搜索), 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 (搜索) is epidemiological: respiratory viruses, predominantly rhinovirus (搜索), 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.
Biomarker Data Support Mechanism
In the completed Phase I study, biomarker analyses in asthma (搜索) 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. The company did not disclose the number of participants in the completed cohorts, adverse-event rates, or quantitative biomarker results, and no quantitative efficacy or detailed safety data were released.
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. RIGImmune (搜索) has reported preclinical activity of the approach against several respiratory RNA viruses, including rhinovirus (搜索), influenza and RSV.
Two-Part Phase I/II Challenge Study Now Recruiting
The next planned study is the RIG 101 Trial in Healthy Adults and Adults With Asthma (搜索), 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 (搜索) challenge study in asthma patients, assessing whether pre-treatment with RIG-101 reduces viral replication or clinical consequences following controlled RV-A16 inoculation. The clinical registry describes the program as targeting 82 participants at two UK sites, with Part B testing RIG-101 against placebo in adults with asthma before and after rhinovirus RV-A16 challenge. The trial is currently recruiting.
The rhinovirus (搜索) challenge model used in Part B is described as 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.
RIGImmune Acquisition Adds SLR Class and Delivery Platform
Leyden Labs acquired RIG-101 through its purchase of RIGImmune (搜索), 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 (搜索). The company confirmed the acquisition in an email to European Biotechnology: "The acquisition is complementary to Leyden's current approach and aligns nicely with the organizational mission. The acquisition occurred in the Spring of 2026."
Public filings provide additional detail. Alembic Pharmaceuticals, an early RIGImmune (搜索) investor, states in its 2025/26 annual report that Leyden acquired RIGImmune under a share purchase agreement dated March 20, 2026. Alembic received 994,615 preferred shares and 1,032,592 common shares in Leyden Labs, valued at $6.68 million, as upfront consideration for its RIGImmune holding, plus undisclosed contingent payments tied to milestones. That figure does not represent the total acquisition price but could point toward a transaction in company shares rather than cash. Alembic had been involved since 2021 with RIGImmune, when its initial investment gave it a 19.97% post-money stake in the company. Leyden Labs did not disclose financial terms of the deal.
RIGImmune (搜索), now a Leyden Labs subsidiary, holds an exclusive license from Yale University (搜索) to develop and commercialize RIG-101. The company was founded in 2020 by Yale professors Anna Marie Pyle and Akiko Iwasaki around stem-loop RNAs targeting RIG-I (搜索). In 2022, it acquired UK respiratory drug-delivery company SubIntro (搜索), combining the RNA technology with what became its NEED delivery platform, alongside financing from F-Prime Capital. RIGImmune later secured an exclusive Yale license covering its stem-loop technology and backing from the Gates Foundation.
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.
Financing Backdrop and Competitive Landscape
The deal came during a period of heavy fundraising for Leyden Labs. In June, the company added €40 million from investors including the EIC Fund, Invest-NL, the Gates Foundation and ClavystBio to fund its mucosal protection platform. That followed a €30 million financing in October 2025, a $70 million Series B earlier that year and €20 million in venture debt from the European Investment Bank.
RIG-101's focus on respiratory protection in asthma (搜索), using an RNA-based intranasal approach, is mechanistically distinct from oncology programs targeting the same pathway. Pfizer licensed RIG-I (搜索) small molecule agonist technology from Kineta (搜索) for oncology in 2018, and TransCode Therapeutics has published preclinical data on a separate RIG-I immunotherapeutic candidate in cancer. No approved RIG-I agonist currently exists in any indication.