Influenza virus delta NS1 vaccine(Avir Green Hills Biotechnology)

Leiden, The Netherlands – 5 June 2023 – A consortium of eight academic and industry partners is advancing the development of a universal influenza vaccine with a €7.6 million grant from the European Union. Through its FLUniversal programme, the consortium will conduct clinical trials of DeltaFLU, a rapid-acting universal influenza vaccine for intranasal administration. FLUniversal also will seek to elucidate molecular and immunological mechanisms of protection, and identify potential new correlates of protection using data from clinical trials and preclinical models. The partners will develop a novel controlled human infection model (CHIM) and influenza challenge strain which they will use to evaluate protective efficacy of DeltaFLU in a clinical challenge study. Ed Schmidt, PhD, Project Manager at consortium member Leiden University Medical Center (LUMC) remarked, “Influenza is a major public health problem globally. A universal influenza vaccine that provides protection against all seasonal influenza strains and emerging strains with pandemic potential is an urgent goal. The FLUniversal consortium unites world-leading experts with the tools and knowledge to develop a novel universal influenza vaccine that already has surmounted key hurdles of novel vaccines: demonstration of safety and robust immunogenicity in humans and manufacturability. Our synergistic combination of preclinical models, a CHIM to produce results similar to wild-type infection, clinical samples, and integrated complex immunological analyses form a unique platform to identify molecular signatures of protection and reduce the timeline and risks involved in clinical development.” DeltaFLU universal influenza vaccine, developed and owned by FLUniversal partner Vivaldi Biosciences, is based on influenza virus strains genetically modified to eliminate the NS1 gene. This genetic modification results in the ability of DeltaFLU to rapidly induce interferon and broadly cross-neutralising antibodies in the nasal passages, generating protection at the point of entry of influenza viruses, and establishing tissue-resident memory T cells for protection against repeat infection. The self-adjuvanting effect of interferon enhances T and B cell activity for a broadly protective systemic immune response. Deletion of NS1 also makes DeltaFLU safe because the genetically modified strains are unable to produce viral progeny and are not shed by vaccine recipients. Vivaldi has demonstrated safety and broad immunogenicity of DeltaFLU vaccine strains in clinical trials, and achieved proof of concept for universal protection against influenza A and B strains in animal models. LUMC and the Centre for Human Drug Research are responsible for the clinical studies in the FLUniversal programme: a Phase 1 study of safety and immunogenicity of DeltaFLU, a clinical study to characterise the novel influenza challenge strain and validate the CHIM, and a clinical challenge study of DeltaFLU in healthy adult volunteers to demonstrate protective efficacy. Vivaldi is responsible for GMP manufacture of the DeltaFLU vaccines and novel challenge strain using its high-yield Vero cell production system. The Medicines and Healthcare Products Regulatory Agency of the UK, participating in FLUniversal as an associate partner, is responsible for the isolation, selection and characterisation of the novel influenza virus challenge strain. MediTox, a GLP-certified contract research organisation with extensive expertise in nonclinical pharmacology and toxicology studies, will conduct the preclinical studies of DeltaFLU. Studies in the ferret model will include evaluations of safety, immunogenicity and challenge-protection. MediTox will further study DeltaFLU in the Syrian golden hamster model to identify immune fingerprints that correlate with protection against transmission of influenza virus from infected to immunised animals. Statens Serum Institut, an infectious disease research institute under the Danish Ministry of Health, will use state of the art techniques to evaluate samples from the preclinical and clinical studies, including cellular analyses of samples from the blood and nasal mucosa, to identify correlates of protection. VisMederi, a leader in validating immunological assay services, with unique competence in GCLPaccredited qualified sample analysis, will carry out integrated complex immunological assays for the identification of molecular signatures of protection. Zafiro Business Solutions, a consulting and advisory organisation specialising in EU programmes, serves as the FLUniversal programme coordinator, with responsibility for project management and compliance with ethics requirements. FLUniversal (Project Name: Intranasal, rapid-acting vaccine for all seasonal and pandemic influenza viruses) is funded under the European Union’s Horizon Europe Framework Programme (HORIZON). For further information, please contact: E.D.L. (Ed) Schmidt, Ph.D. Project Manager Department of Medical Microbiology Leiden University Medical Center e.d.l.schmidt@lumc.nl Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HADEA). Neither the European Union nor HADEA can be held responsible for them.

FORT COLLINS, Colorado and VIENNA, Austria – July 20, 2021 – Vivaldi Biosciences, a clinical-stage biotechnology company developing genetically engineered intranasal vaccines for viral respiratory diseases, today announced positive preclinical data supporting further development of Delta-19, its combination vaccine for protection against COVID-19 and all strains of influenza. SARS-CoV-2, the virus responsible for COVID-19, is expected to become endemic and adopt a seasonal pattern, much like influenza. Delta-19 is designed to address the dual disease threats of Covid-19 and influenza with a superior approach for greater protection against both diseases. Studies of Delta-19 in the ferret model showed that 100% of the immunized animals generated high titers of SARS-CoV-2 spike-specific neutralizing antibodies, and 100% of the immunized animals were protected against challenge with a wild-type strain of SARS-CoV-2. Importantly, immunized ferrets had negligible amounts of SARS-CoV-2 challenge virus in their noses and mouths, while the virus proliferated to high levels in the noses and mouths of control ferrets. These findings suggest the possibility of achieving sterilizing immunity with Delta-19, preventing replication of SARS-CoV-2 in the upper respiratory tract and transmission to other individuals. Vivaldi Biosciences already has shown in clinical trials that the influenza vaccine component of Delta-19 is safe, immunogenic, and generates broadly cross-protective antibodies to diverse influenza strains. Delta-19 builds on Vivaldi Biosciences’ DeltaFLU universal influenza vaccine, which has been successfully evaluated in four Phase 1 and 2 clinical trials. DeltaFLU shows potential for universal protection against all influenza A and B virus strains, including drifted seasonal influenza strains and emerging pandemic strains. “With these strong proof of concept data we are ready to advance our Delta-19 program toward clinical trials. We filed a patent application last year, and we are prepared to undertake an accelerated development program, employing our expertise in vaccine strain optimization and cell-based production, and ready access to BSL-3 facilities,” said Bill Wick, CEO of Vivaldi Biosciences. Delta-19 and DeltaFLU are based on Vivaldi Biosciences’ Delta NS1 vaccine vector. Delta-19 is a chimeric SARS-CoV-2 Delta NS1 vaccine that expresses key immunogenic antigens of SARS-CoV-2 and influenza viruses. Upon intranasal administration, Delta NS1 vaccines rapidly induce the immune signaling protein interferon and IgA antibodies to neutralize viruses in the nasal passages. Interferon generates a selfadjuvant effect that activates CD4+ and CD8+ T cells and antibody-producing B cells for robust systemic immunity. Delta-19 may provide important advantages over mRNA vaccines for Covid-19. Unlike mRNA vaccines, which are administered by intramuscular injection, intranasal administration of Delta-19 is needle-free and pain-free. Reactogenicity and side effects of mRNA vaccines may impair patient acceptance. In contrast, clinical trials Delta NS1 vaccines show only mild side effects in some recipients. The stringent and expensive cold chain requirements of mRNA vaccines will not apply to Delta NS1 vaccines. About Vivaldi Biosciences Vivaldi Biosciences is developing genetically engineered intranasal vaccines for epidemic and pandemic viral respiratory diseases. The company’s lead vaccine candidates are its Delta-19 combination Covid-19 + universal influenza vaccine in preclinical development, and its DeltaFLU universal influenza vaccine in Phase 2 clinical development. Vivaldi Biosciences’ vaccine candidates are based on the company’s proprietary Delta NS1 technology platform. Delta NS1 vaccines have the unique ability to induce interferon, a signaling protein in the body that triggers a broad-based response from multiple components of the immune system. Upon intranasal administration of Delta NS1 vaccines, rapid induction of interferon and broadly neutralizing antibodies generates a first line of defense in the nasal passages, the point of entry of respiratory viral pathogens. The self-adjuvanting effect of interferon also creates a second line of defense, activating T cells and antibody-producing B cells for a broadly protective systemic immune response. Vivaldi Biosciences has developed a rapid, high-yield Vero-cell based manufacturing system and produced Delta NS1 vaccines under cGMP for clinical trials. Vivaldi Biosciences is a venture-backed company with operations at the Research Innovation Center at Colorado State University, Fort Collins, CO, and in Vienna, Austria. NGN Capital LLC is the company’s lead investor. Learn more at and connect with Vivaldi Biosciences on Linkedin. Contact Bill Wick, CEO, Vivaldi Biosciences Tel: +1 650-400-8915 bill.wick@vivaldibiosciences.com Forward-Looking Statements This release contains forward-looking statements relating to Vivaldi Biosciences, which are not historical facts and are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements included in this communication concerning activities, events or developments that we expect, believe or anticipate will or may occur in the future are forward-looking statements. 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