AZD7442 long-acting antibody combination Phase III PROVENT trial prevention data to be presented in late-breaker session

AZD1222 Phase III analysis investigating asymptomatic infection and duration of viral shedding in infections will also be presented

AstraZeneca will present data across its COVID-19 and respiratory syncytial virus (RSV) pipeline at the 10^th Annual IDWeek Virtual Conference, September 29 to October 3, 2021, illustrating its commitment to advancing innovative science in infectious diseases.

Data featuring AstraZeneca’s investigational long-acting antibody (LAAB) programs – AZD7442 for COVID-19 and nirsevimab for RSV – as well as AZD1222, will be presented as three late-breaking oral presentations.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “The compelling data being presented at IDWeek reflect our scientific advances across infectious diseases in response to the COVID-19 pandemic and surges in respiratory syncytial virus cases. Our PROVENT Phase III data demonstrate AZD7442 may offer much-needed protection for vulnerable populations who may not mount an adequate immune response to COVID-19 vaccination.”

Advancing COVID-19 prevention with cutting-edge science

High-level efficacy and safety data from the PROVENT Phase III trial investigating AZD7442 for prevention of COVID-19 will be presented for the first time following the initial announcement in August. The data showed that AZD7442 compared to placebo achieved a statistically significant reduction in the risk of developing symptomatic COVID-19 prior to virus exposure (pre-exposure prophylaxis).¹ More than 75% of participants in the trial had co-morbidities, which includes those with a reduced immune response to vaccination.¹ In PROVENT, the LAAB was well tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.

A late-breaker oral presentation of Phase III results will show whether AZD1222 prevents asymptomatic cases of COVID-19, as well as its capability to shorten viral shedding in breakthrough infections. Understanding the duration of viral shedding may help the implementation of effective public health efforts to control the spread of the virus.²

Late breaking data on nirsevimab

The MELODY Phase III trial data for nirsevimab, an investigational long-acting antibody being developed by AstraZeneca and Sanofi, will demonstrate the potential of nirsevimab to help protect all infants entering their first RSV season with a single dose.

Key AstraZeneca presentations during IDWeek 2021

AZD7442

AZD7442 is a combination of two LAABs - tixagevimab (AZD8895) and cilgavimab (AZD1061) - derived from B-cells donated by convalescent patients after SARS-CoV-2 virus.^3-4 Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June 2020, the human monoclonal antibodies bind to distinct sites on the SARS-CoV-2 spike protein^4-5 and were optimized by AstraZeneca with half-life extension and reduced Fc receptor and complement C1q binding. The half-life extension more than triples the durability of its action compared to conventional antibodies and could afford up to 12 months of protection from COVID-19 following a single administration.^6-9 The reduced Fc receptor binding aims to minimize the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.¹⁰

AZD7442 is being studied in a comprehensive clinical trial program for both prevention and treatment of COVID-19. In August 2021, AstraZeneca announced positive high-level results from the PROVENT Phase III pre-exposure prophylaxis trial. Other ongoing trials include TACKLE COVID-19¹¹, a Phase III mild-to-moderate COVID-19 outpatient treatment trial, and collaborator treatment trials in outpatient and hospitalized settings.

Preliminary ‘in vitro’ findings demonstrate that AZD7442 neutralizes recent emergent SARS-CoV-2 viral variants, including the Delta and Mu variants.^12,13

AstraZeneca is preparing regulatory submission of the prophylaxis data to health authorities for potential emergency use authorization or conditional approval of AZD7442.

AZD1222

AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

AZD1222 has been granted a conditional marketing authorization or emergency use in more than 80 countries across six continents. More than 1.1 billion doses of AZD1222 have been supplied to more than 170 countries worldwide, including more than 100 countries through the COVAX Facility.

Nirsevimab

Nirsevimab is an investigational long-acting antibody, being developed by AstraZeneca and Sanofi using AstraZeneca’s proprietary YTE technology, designed to protect all infants for the RSV season. Due to its extended half-life technology, nirsevimab is being developed as a single dose for all infants experiencing their first RSV season and infants with congenital heart disease or chronic lung disease entering their first and second RSV season.¹⁴ The current anti-RSV antibody, AstraZeneca’s Synagis, is limited to high-risk infants and provides one-month protection, requiring five injections to cover an RSV season.¹⁵

Nirsevimab is designed to provide RSV protection to all infants via an antibody given directly to an infant to help prevent LRTI caused by RSV. Unlike an active immunization, monoclonal antibodies do not require the activation of the immune system to help offer rapid and direct protection against disease.¹⁶ There has been a recent resurgence of RSV during the easing of COVID-19 public health measures.¹⁷

Nirsevimab has been granted regulatory designations to facilitate expedited development by three major regulatory agencies around the world. These include Breakthrough Therapy Designation by The China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the US Food and Drug Administration; and access granted to the European Medicines Agency PRIority MEdicines (PRIME) scheme. Nirsevimab is currently under clinical investigation and has not been approved by any regulatory authority.

In March 2017, AstraZeneca and Sanofi announced an agreement to develop and commercialize nirsevimab. Under the terms of the agreement, AstraZeneca leads all development and manufacturing activities and Sanofi will lead commercialization activities and record revenues. Under the terms of the global agreement, Sanofi made an upfront payment of €120m, has paid a development milestone of €30m and will pay up to a further €465m upon achievement of certain development and sales-related milestones. The two companies share all costs and profits. Revenue from the agreement is reported as Collaboration Revenue in the Company’s financial statements.

Related, in November 2018, AstraZeneca divested US commercial rights for Synagis to Swedish Orphan Biovitrum AB (publ) (Sobi) in addition to the right to participate in payments that may be received by AstraZeneca from the US profits or losses for nirsevimab. Under the agreement, AstraZeneca received upfront consideration of $1.5bn, consisting of $1.0bn in cash and $500m in ordinary shares of Sobi upon completion, and will have received a total of $60m in non-contingent payments for nirsevimab during 2019-2021. AstraZeneca will also receive up to $470m in sales-related payments for Synagis, a $175m milestone following the submission of the Biologics License Application (BLA) for nirsevimab and potential net payments of approximately $110m on achievement of other nirsevimab profit and development-related milestones. Upon payment of the $175m milestone on BLA submission, Sobi’s ongoing participation will amount to AstraZeneca’s full share of profits or losses under the agreement with Sanofi for nirsevimab in the US. AstraZeneca will continue to manufacture and supply nirsevimab globally and is entitled to an additional royalty from Sobi if profits from nirsevimab in the US exceed a pre-specified level.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

References

1. AstraZeneca news release. AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/azd7442-prophylaxis-trial-met-primary-endpoint.html. [Last accessed: September 2021]
2. Public Health England. COVID-19 vaccine surveillance report Week 27. 2021 Jul. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1000512/Vaccine_surveillance_report_-_week_27.pdf [Last accessed: September 2021]
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8. Yu XQ, et al. Safety, Tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrob Agents Chemother. 2016; 61 (1): e01020-16.
9. Domachowske JB, et al. Safety, tolerability and pharmacokinetics of MEDI8897, an extended half-life single-dose respiratory syncytial virus prefusion F-targeting monoclonal antibody administered as a single dose to healthy preterm infants. Pediatr Infect Dis J. 2018; 37(9): 886-892.
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