PfizerPfizer Inc. (NYSE: PFE, "Pfizer") and BioNTech SE (Nasdaq: BNTX, "BioNTech") announced top-line results from their Phase 3 clinical trial to evaluate the companies' combined mRNA vaccine candidate against influenza and COVID-19 in healthy individuals 18-64 years of age. The combination candidate consists of Pfizer's mRNA-based influenza vaccine candidate with the companies' licensed COVID-19 vaccine. The Phase 3 trial measured two primary immunogenicity objectives (immunogenicity against SARS-CoV-2 as well as immunogenicity against influenza A and B), of which one was met. In a separate Phase 2 trial, Pfizer evaluated trivalent ("tIRV") influenza mRNA standalone vaccine candidates which demonstrated robust immunogenicity in individuals 18-64 years of age. The companies are evaluating adjustments to the combination vaccine candidate aimed at improving immune responses against influenza B and will discuss next steps with health authorities.

Update on Phase 3 Pfizer and BioNTech Combination Vaccine Trial

The Phase 3 randomized, observer-blinded study ( NCT06178991) enrolled more than 8,000 adults 18 through 64 years of age to evaluate the safety, tolerability, and immunogenicity of a single dose combination vaccine candidate against influenza and COVID-19. In this clinical trial, the vaccine candidate was compared to a licensed influenza vaccine and the companies' licensed COVID-19 vaccine given at the same visit. The primary immunogenicity objectives were to demonstrate that the antibody responses to influenza (hemagglutination inhibition, "HAI") and to SARS-CoV-2 (neutralizing titer, "NT") elicited by the combination vaccine candidate were non-inferior ("NI") to standard of care ("SOC"). Compared to a licensed influenza vaccine, the tIRV formulation was noteworthy for eliciting robust influenza A responses, including a continued trend of higher influenza A responses versus a licensed influenza vaccine, while it showed lower geometric mean titers ("GMT") and seroconversion against the influenza B strain. In addition, the formulation demonstrated comparable responses against SARS-CoV-2 versus the companies’ licensed COVID-19 vaccine. No safety signals with the combination vaccine have been identified in an ongoing safety data review. Participants who received a licensed influenza and COVID-19 vaccine with co-administration continued to elicit robust immune responses against both influenza and COVID-19 with no safety signals identified to date.

"We are encouraged by the robust immunogenicity we saw with our combination vaccine against influenza A, which was similar to what we had seen for our initial quadrivalent influenza vaccine where we saw superior relative vaccine efficacy against a comparator flu vaccine," said Annaliesa Anderson, PhD, Senior Vice President and Head, Vaccine Research and Development at Pfizer. "We are committed to developing vaccines that will reduce the burden of respiratory diseases and believe that combination vaccines are the most efficient way to do this. Today's results provide insight and direction towards achieving this goal, and we remain optimistic about our combination COVID-19 and influenza program, for which we are evaluating the next steps."

"We are dedicated to developing combination vaccines which provide broader protection against multiple respiratory diseases," said Prof. Ugur Sahin, M.D., CEO and Co-founder of BioNTech. "The insights gained from this combination vaccine trial are highly valuable and will play a crucial role in guiding the further development of Pfizer's and our combination vaccine program against influenza and COVID-19. We are committed to drawing on our experience in developing mRNA-based vaccine candidates against multiple antigens and believe we can successfully accomplish this task in collaboration with our partner Pfizer."

Update on Pfizer's Phase 2 Second Generation Influenza Vaccine Trial

Pfizer's Phase 2 trial ( NCT06436703) to evaluate second-generation candidates against influenza was initiated earlier this year and enrolled 450 participants 18-64 years of age, who were randomized to receive investigational mRNA-based influenza vaccines or influenza vaccines approved by the U.S. Food and Drug Administration ("FDA"). As previously stated, Pfizer announced positive top-line Phase 3 results from its first-generation quadrivalent ("qIRV") vaccine candidate which achieved the first and only demonstration of efficacy for an mRNA vaccine in a group of study participants 18-64 years of age. The primary endpoints for this qIRV first-generation candidate were not met in adults aged 65 and older, as statistical non-inferior relative vaccine efficacy ("rVE") compared to a licensed influenza vaccine was not met based on the number of cases accrued. Pfizer developed second-generation candidates with the goal of improving immunogenicity and potentially breadth of protection, including new tIRV formulations that matched updated recommendations by the World Health Organization ("WHO") and the FDA's Vaccines and Related Biological Products Advisory Committee ("VRBPAC"). The tIRV formulations elicited robust influenza A responses and B responses, including continued trend of higher influenza A responses versus a licensed influenza vaccine. There were no safety signals reported. Data from this Phase 2 trial for adults 65 years of age and older will become available at a later date.

Pfizer will also continue to evaluate its influenza vaccine program and discuss next steps with health authorities.

About Influenza

Influenza causes an estimated 140,000 to 710,000 hospitalizations, 12,000 to 52,000 deaths(1) and about $25 billion in economic loss(2) in the U.S. each year. People 65 and older are at increased risk of serious complications from influenza, including hospitalization and death.(3) Even when a vaccine matches circulating strains well, current influenza vaccines typically confer 40% to 60% protection each year, with even lower protection in years with poor matching of strains.(4) The impact of influenza on racial and ethnic minority groups in the U.S. is even larger. Black Americans are nearly two times more likely than their white counterparts to be hospitalized for influenza while Latino and Indigenous Americans are 1.2 and 1.3 times more likely, respectively.(5)

With circulating influenza strains continually changing, predicting the best match for the next season's vaccine is difficult for global health experts as those strains are chosen more than six months before the start of the flu season that they target. The flexibility of mRNA technology and its rapid manufacturing could potentially allow better strain matches in future years, and in a pandemic influenza situation, mRNA technology could enable rapid, large-scale manufacturing of vaccines.

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About Pfizer: Breakthroughs That Change Patients' Lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us.

About BioNTech

Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron.

1. Disease Burden of Flu. Centers for Disease Control & Prevention. Available at https://www.cdc.gov/flu/about/burden/index.html
2. Putri et al, Vaccine. 2018 Jun 22;36(27):3960-3966. doi: 10.1016/j.vaccine.2018.05.057
3. Flu & People 65 Years and Older. Centers for Disease Control and Prevention. Available at: Flu & People 65 Years and Older | CDC
4. Vaccine Effectiveness: How Well do the Flu Vaccines Work? Centers for Disease Control & Prevention. Available at https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm
5. Flu Disparities Among Racial and Ethnic Minority Groups CDC. Available at https://www.cdc.gov/flu/highrisk/disparities-racial-ethnic-minority-groups.html