The Phase 1 clinical trial for ARCT-2304, a self-amplifying mRNA vaccine, seeks to address pandemic influenza risk as H5N1 cases increase.
Human cases in the US.
Image credits: CDC
Arcturus Therapeutics has initiated a Phase 1 clinical trial of ARCT-2304, also known as LUNAR-H5N1, a self-amplifying mRNA (sa-mRNA) vaccine designed to prevent pandemic influenza caused by the H5N1 virus. The trial, which began in December 2024 with the first participant, is being conducted across multiple US sites and will enroll 200 healthy adults. The study will evaluate the safety and immune response of varying doses and vaccination schedules, with interim results expected in the second half of 2025.1
LUNAR-H5N1 leverages Arcturus' proprietary LUNAR delivery and STARR mRNA platforms, which have previously demonstrated the ability to elicit strong immune responses at low doses, along with prolonged neutralizing antibody persistence. Funded by the Biomedical Advanced Research and Development Authority (BARDA), the trial will assess immune responses in both younger adults (ages 18-59) and elderly participants (ages 60-80), who are at higher risk for influenza complications. Researchers will measure immune responses through hemagglutination inhibition, virus neutralization, and enzyme-linked lectin assays.1
“The clinical validation of our low-dose STARR mRNA technology for H5N1 is a critical step toward enhancing global pandemic preparedness,” said Joseph Payne, president and CEO of Arcturus Therapeutics. “We are working closely with our partners, BARDA and CSL, to advance this effort worldwide.”1
In an exclusive email interview with Neda Safarzadeh, VPand head of investor relations, public relations, and marketing at Arcturus Therapeutics, she answered key questions about LUNAR-H5N1 and its potential in addressing the global threat of H5N1 avian influenza.
Neda Safarzadeh
Image credits: LinkedIn
Contagion: How does LUNAR-H5N1 address concerns surrounding H5N1 avian influenza?
Safarzadeh: "LUNAR-H5N1 is a prophylactic vaccine designed to protect against bird flu infection. Its low-dose formulation enables more cost-efficient stockpiling, supporting global pandemic preparedness efforts."
Contagion: What advantages does the self-amplifying mRNA platform in LUNAR-H5N1 offer compared to traditional influenza vaccines?
Safarzadeh: "LUNAR-H5N1's self-amplifying mRNA platform enhances immune response and offers better liver durability, providing a more robust and lasting defense compared to conventional vaccines."
Contagion: Given the rise in H5N1 cases in animals and humans, how does the partnership with BARDA aid in the global rollout of LUNAR-H5N1?
Safarzadeh:"With CSL's extensive global reach, a successful Phase 1 trial in the US. (funded by BARDA) will enable a smoother global rollout, particularly with CSL’s support to expand efforts beyond the US."
This announcement comes amid growing concerns about H5N1, which has been linked to severe human infections and deaths, especially among those exposed to infected poultry. The recent death of the first US patient from H5N1, a Louisiana resident with underlying health conditions, highlights the ongoing threat. The fatality, caused by the more virulent D11 genotype, underscores the need for continued vigilance, though no person-to-person transmission has been detected.2
As of December 28, 2024, over 12,400 individuals have been monitored for potential exposure to infected animals, including birds, poultry, and dairy cows. Among these, 7,300 exposures were linked to dairy cows, and 5,100 to birds and other animals, including poultry. Additionally, 560 people have been tested for novel influenza A, including H5N1, since March 24, 2024. Of those, 160 were exposed to dairy cows and 400 to birds or poultry.3
Arcturus has started a Phase 1 clinical trial of its ARCT-2304 vaccine to prevent H5N1 influenza, with 200 healthy adults enrolled.
The trial will assess safety and immune response using Arcturus' LUNAR delivery and STARR mRNA platforms.
The trial is funded by BARDA and conducted in collaboration with CSL to support pandemic preparedness.
California has reported the majority of the confirmed human cases of H5N1 in the US As of the latest reports, there have been 37 human exposure incidents in the state, mostly linked to commercial agriculture and animal operations, with one case having an unknown source.3 In response to the outbreak, Governor Gavin Newsom declared a state of emergency, emphasizing the need for government agencies to have the necessary resources and flexibility to respond effectively. This action follows the detection of bird flu cases in dairy cows. While the risk to the public remains low, state officials are focused on strengthening public health efforts and monitoring systems.4
As H5N1 cases rise, Arcturus Therapeutics' Phase 1 trial for LUNAR-H5N1 aims to improve pandemic preparedness. The vaccine could strengthen vaccine supply and distribution. While the public risk remains low, ongoing monitoring and vaccine development are essential. The trial's results may provide key data for future influenza responses.
