The US government is laying out around $1/2 billion in new funding for a rapidly advanced antibody drug combination from Cambridge UK Big Bio business AstraZeneca.

This deal for AstraZeneca’s COVID-19 Long-Acting AntiBody (LAAB) combination AZD7442 follows the treatment’s surge into Phase III clinical trials.

It is worth around $486 million but, as Business Weekly previously reported, the Cambridge company had previously earned $25m from US government agencies BARDA and the Defense Advanced Research Projects Agency for the discovery and evaluation of the monoclonal antibodies, as well as the Phase I clinical trial started in August to assess safety, tolerability and pharmacokinetics of AZD7442 in healthy individuals. That takes the US government haul for AZ to $511m.

AstraZeneca reveals that two Phase III clinical trials of AZD7442 will start in the next few weeks. One will enrol over 6,000 adults for the prevention of COVID-19 with additional trials enrolling around 4,000 adults for the treatment of SARS-CoV-2 infections.

The LAABs have been engineered with AstraZeneca’s proprietary half-life extension technology to increase the durability of the therapy for six to 12 months following a single dose. 

The combination of two LAABs is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus.

AstraZeneca plans to supply up to 100,000 doses starting towards the end of 2020 and the US Government can acquire up to an additional one million doses in 2021 under a separate agreement.

Pascal Soriot, AstraZeneca’s chief executive officer, said: “This agreement with the US Government will help accelerate the development of our long-acting antibody combination which has the potential to provide immediate and long-lasting effect in both preventing and treating COVID-19 infections. 

“We will be evaluating the LAAB combination in different settings from prophylaxis, to outpatient treatment to hospitalisation, with a focus on helping the most vulnerable people.”

LAABs mimic natural antibodies and have the potential to treat and prevent disease progression in patients already infected with the virus, as well as to be given as a preventative intervention prior to exposure to the virus. 

A LAAB combination could be complementary to vaccines as a prophylactic agent, e.g. for people for whom a vaccine may not be appropriate or to provide added protection for high-risk populations. It could also be used to treat people who have been infected.

The fresh US government agreement is not anticipated to impact AstraZeneca’s financial guidance for 2020 as the US Government funding is being offset by expenses to progress the clinical trials of AZD7442 as well as manufacturing process and upscaling costs. 

Should the Phase III trials prove successful and AZD7442 become an approved medicine the company anticipates providing doses at commercial terms during and after the current coronavirus pandemic.

AZD7442 is a combination of two LAABs derived from convalescent patients after SARS-CoV-2 infection. Discovered by Vanderbilt University Medical Center and licensed to AstraZeneca in June, the LAABs were optimised by AstraZeneca with half-life extension and reduced Fc receptor binding.
The half-life extended LAABs should afford six to 12 months of protection from COVID-19.

The reduced Fc receptor binding aims to minimise the risk of antibody-dependent enhancement of disease – a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.

In a recent Nature publication, the LAABs were shown in pre-clinical experiments to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.