Vivaldi Biosciences Presents Data at the World Vaccine Congress Demonstrating Potential of deltaFLU as Universal Influenza Vaccine

deltaFLU Outperformed Licensed Vaccine Against Drifted and Shifted Influenza Strains

Vivaldi Biosciences announced that Thomas Muster, PhD, Chief Scientific Officer, will deliver a presentation today on the company's clinical-stage deltaFLU universal influenza vaccine candidate at the World Vaccine Congress in Washington, DC. Dr. Muster will present data from a new nonclinical study showing that deltaFLU provided protection against distantly drifted and shifted influenza strains, while a leading licensed influenza vaccine lacked protection agains these unmatched strains.

Currently licensed influenza vaccines generally rely on an antigenic match between vaccine strains and circulating strains for protective efficacy. Mismatches between vaccine and circulating strains frequently occur, reducing vaccine effectiveness. Overall effectiveness of available influenza vaccines typically is just 40-60%. The US Centers for Disease Control and Prevention (CDC) reports overall influenza vaccine effectiveness of 36% for the current flu season, with effectiveness of only 25% for influenza A/H3N2, the strain causing most influenza infections.

Vivaldi's nonclinical study demonstrated that deltaFLU provided protection against influenza A and B strains with significant antigenic differences from the strains comprising the deltaFLU vaccine. In particular, the study showed that a single immunization with deltaFLU containing the 2017-2018 influenza A/H1N1 vaccine strain providede statistically significant measures of protection against an A/H1N1 strain that circulated before the 2009 influenza A/H1N1 pandemic. These data indicate the potential of a single dose of deltaFLU to protect against an antigenically shifted influenza strain. Antigenic shift is an infrequent, abrupt, and major genetic change generating an influenza strain with new viral surface antigens to which most people have no immunity. The 2009 influenza A/H1N1 pandemic was the result of an antigenic shift.

Vivaldi's study evaluated deltaFLU in comparison with a licensed vaccine and placebo in an established model of human influenza infection, the ferret. The deltaFLU and licensed vaccine contain the three of four influenza vaccine strains, respectively, recommended by the World Health Organisation for the current influenza season. Immunized ferrets were challenges by intranasal administration of an influenza A/H1N1, A/H3N2, or B strain that circulated in 2008 and 2009. These challenge strains represent the problems of influenza antigenic ashift and antigenic drift for vaccine effectiveness. Drifted strains, the result of mutations in the viral surface antigens, may lead to mismatches and reduced effectiveness of conventional influenza vaccines. The A/H3N2 challenge strain in the study has six antigenic drifts from the A/H3N2 vaccine strain, and the B challenge strain has three antigenic drifts from its vaccine strain counterpart. The A/H1N1 challenge strain is antigenically shifted from the A/H1N1 vaccine strain.

deltaFLU showed protection against all three challenge strains, as indicated by established parameter of influenza infection including fever and shedding of challenge virus. Ferrets immunized with a single dose of deltaFLU had statistically significant recutions in body temperature and titer of shed challenge virus. Only 2 of the 24 ferrets immunized with deltaFLU and subsequently challenged with 1 of the 3 unmatched strains reached body temperatures indicating moderate fever (40.0-40.4°C). In contrast, the licensed vaccine generally failed to protect immunized and challenged anmials from fever. Fourteen of the 24 ferrets immunized with the licensed vaccine exhibited fever (>=40.0°C) after challenge, including 6 ferrets that exhibited severe fever (>=40.5°C).

Lack or reduction of shedding of challeng virus is another measurable indicator of protection against influenza infection. deltaFLU showed greater protection versus the licensed vaccine in evaluations of shedding of the A/H1N1 and B challenge viruses. Moreover, the virus shedding data corroborated the fever data for ferrets in the A/H1N1 and B challenge groups. The A/H3N2 strain was a low-shedding virus in all groups; however, this challenge strain produced fever >=40.0°C in 7 out of 8 animals in the licensed vaccine group and in only 1 out of 8 animals in the deltaFLU group. Other symptoms of influenza infection, such as sneezing and nasal discharge, were in line with the findings on fever and shedding.

Data from completed clinical and nonclinical studies of deltaFLU demonstrate protective mechanisms against a broad range of influenza A and B strains, and indicate the potential of deltaFLU as a universal influenza vaccine. deltaFLU has been evaluated successfully in Phase 1 and 2 clinical studies and has been shown in humans to be safe and immunogenic. Moreover, in study volunteers deltaFLU has been shown to induce IgA antibodies that cross-neutralize influenza strains with significan antigenic differencest from strains in the deltaFLU vaccine. For example, a deltaFLU vaccine strain of subtype A/H1N1 induced human local nasal IgA antibodies that neutralize influenza viruses of the A/H3N2 and A/H5N1 subtypes.

deltaFLU is produced in Vivaldi's high-yield Vero cell production process. Vero cells are an established production substrate for human vaccines. Vivaldi's Vero cell process generally takes approximately 12 weeks from strain selection to product releas for clinical use. Traditional egg based production may take up to 6 months, and may induce antigenic changes that reduce vaccine efficacy.

About Vivaldi Biosciences

Vivaldi Biosciences is developing its deltaFLU influenza vaccine to provide broad cross-protection and superior efficacy in the prophylaxis of seasonal and pandemic influenza. deltaFLU is composed of influenza vaccine strains genetically modified by deletion of the gene for nonstructural protein 1 (NS1). This protein blocks interferon, a key component of the immune system's response to viral infection. Since deltaFLU strains lack the ability to suppress the host interferon response, they induce high levels of interferonm achieving a natural adjuvant effect that stimulates the immune system's T cells and antibody-producing B cells. Administered as a nasal spray, deltaFLU generates a first line of defense at the point of entry of circulating viruses. In clinical trials, deltaFLU has been shown to induce antibodies in the nasal mucosa that cross-neutralize influenza strains of different subtypes; for example, the deltaFLU A/H1N1 vaccine stain induces mucosal antibodies that neutralize influenza viruses of the A/H3N2 and A/H5N1 subtypes. deltaFLU strains are replication-deficient in animals and humans and are not shed by the recipient, providing significant safety advantages. Vivaldi Biosciences is based at the Research Innovation Center at Colorado State University and in Vienna, Austria. Additional information about Vivaldi can be found at www.vivaldibiosciences.com.