FluGen Announces Publication of Positive Results from Phase 2 Human Challenge Study of Its M2SR Vaccine Candidate Against Highly Drifted Strain of H3N2 Influenza Virus

– Data published in the Journal of Infectious Diseases demonstrate that M2SR can protect against a multi-seasonal, seven-year drifted influenza strain –

MADISON, Wis., Aug. 2, 2021 /PRNewswire/ — FluGen, Inc., a clinical-stage vaccine company transforming vaccine efficacy in infectious respiratory diseases, today announced the publication of results from its Phase 2 human challenge study of Bris2007 M2SR, the Company’s investigational, supra-seasonal, live, single-replication, intranasal influenza (flu) vaccine. Results published in the Journal of Infectious Diseases show that subjects with vaccine-induced neutralizing antibodies were protected against infection and illness following challenge with an antigenically distinct virus. This is believed to be the first demonstration of vaccine-induced protection against a highly drifted H3N2 influenza virus in a human challenge study.

“Current vaccines are strain-specific and in recent years they have had low efficacy against H3N2 influenza, especially when the vaccine is mismatched to circulating virus,” said Dr. Robert Belshe, the Diana and J. Joseph Adorjan Endowed Professor of Infectious Diseases and Immunology, Emeritus, at Saint Louis University, and Chair of the FluGen Clinical Advisory Board. “The M2SR vaccine candidate is designed to induce a broad, multi-effector immune response, and this study demonstrated that subjects with vaccine-induced neutralizing antibodies were protected against infection and illness following challenge with an antigenically drifted virus. Inactivated vaccines have not had that broad protection. This is the first demonstration in adults of vaccine-induced protection against a highly drifted H3N2 challenge virus.”

In the challenge study, adults 18-55 years of age were randomized to receive a single intranasal spray, either with placebo or with a 10⁸ TCID₅₀ dose of monovalent H3N2 M2SR vaccine. Four weeks later they were challenged with an influenza strain seven years drifted from the vaccine, a period during which WHO recommended four H3N2 vaccine strain changes to maintain match against seasonal influenza virus. Challenge study results demonstrated that, despite the significant mismatch of vaccine and challenge strains, a single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR subjects were infected after challenge, compared to 71% of placebo subjects. The subset of M2SR subjects with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs. 71% of placebo subjects, P=0.0505) and reduced illness.

Adverse events (AE) following vaccination were mild and similar in frequency between placebo and M2SR recipients. Most treatment emergent adverse events (TEAE) were mild in severity, and no vaccine virus shedding was detected in any of the subjects. The correlation between serum markers and efficacy in the trial is expected to accelerate further development of M2SR.

FluGen is has completed evaluating higher doses of M2SR, up to 10⁹ TCID₅₀, in a Phase 1b dose escalation study. Topline results demonstrate that a higher dose of M2SR induced protective immune responses among a higher proportion of recipients than observed with 10⁸ TCID₅₀ in the challenge study.

“The need to frequently change the strains of influenza in the annual flu vaccine due to drift and frequent antigenic mismatch is a significant problem that leads to decreased vaccine effectiveness,” said Paul Radspinner, President and Chief Executive Officer, FluGen, Inc. “This study of our investigational M2SR vaccine at a relatively low dose showed, for the first time, protection against a highly mismatched influenza virus. This is a substantial advancement towards demonstrating the breadth of protection that would be needed to develop a universal vaccine that could be effective against flu viruses that have significantly drifted from the strains contained in the vaccines. The results of the Phase 1b dose escalation study of M2SR showed a substantial increase in immune responses amongst an even broader group of subjects.”

This Phase 2 human challenge study, entitled “Single Replication M2SR Influenza Vaccine Induced Immune Responses Associated with Protection Against Human Challenge with Highly Drifted H3N2 Influenza Strain”, was a proof-of-concept study designed to confirm the safety and tolerability of M2SR, evaluate the protective effect of M2SR against a significantly drifted challenge virus, evaluate challenge virus shedding, and assess correlations between vaccine immunogenicity results and challenge virus infection. The blinded, randomized, placebo-controlled study was conducted in Antwerp, Belgium (EudraCT#: 2017-004971-30; https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004971-30/results).

The study was supported by a $15.4 million grant from the Department of Defense. The U.S. Army Medical Research Acquisition Activity was the awarding and administering acquisition office and this work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Medical Research Program, under Award No. W81XWH-17-1-0430. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.