US FDA authorises phase 1 trial of ImmunityBio’s COVID-19 vaccine candidate hAd5

ImmunityBio announced it has received authorisation from the US Food and Drug Administration (FDA) to begin a Phase I clinical trial of hAd5-COVID-19, the company’s novel COVID-19 vaccine candidate that targets both the inner nucleocapsid (N), engineered to activate T cells, and outer spike (S) protein, engineered to activate antibodies against the coronavirus (SARS-CoV-2). These dual constructs (bivalent sequences) of SARS-CoV-2 offer the potential for the hAd5 vaccine to provide recipients with durable, long-term cell-mediated immunity with potent antibody stimulation against both the S and N proteins. The company anticipates launching a Phase I trial at Irvine, California-based Hoag Hospital this month with adult subjects up to age 55.

“While there are a number of vaccine candidates in development, we believe most are limited by their sole focus on antibody responses to the monovalent spike protein, which may be insufficient to activate the full potential of the immune system to fight the coronavirus. By targeting the nucleocapsid protein on the interior of the virus particle as well as the spike protein on the virus’s surface, we believe this vaccine can stimulate both T-cell-mediated and antibody-mediated immunity to SARS-CoV-2,” said Dr Patrick Soon-Shiong, Chairman and CEO of ImmunityBio.

“The hAd5-COVID-19 vaccine candidate is a novel, engineered, second-generation human adenovirus serotype 5 vaccine. Because it delivers both the S and N proteins, the vaccine has the potential to enable recipients to develop immune “memory”, promoting long-lasting immunity to SARS-CoV-2. The N protein has been engineered with a novel signalling domain to enhance T cell activation. The hAd5 vaccine with this Enhanced T cell Signaling Domain (ETSD) has generated potent CD4+ and CD8+ COVID specific T cell activation recognising S and N following hAd5 vaccination in pre-clinical studies,” informed the company through a statement.

ImmunityBio plans to administer the hAd5-COVID-19 vaccine both as a prime and boost to sustain protection against SARS-CoV-2 since multiple re-immunizations using the same vector platform are now possible with the novel hAd5 platform. The company is also pursuing preclinical development for oral, inhalational and intranasal administration to provide mucosal immunity in addition to durable humoral and cell-mediated immunity against COVID-19.

Under the terms of a definitive agreement announced on August 24, 2020, ImmunityBio and its affiliate NantKwest agreed to share equally the costs of development, manufacturing, marketing and commercialisation of the products each is developing related to COVID-19, including the hAd5 vaccine candidate.

In addition to the vaccine candidate, the agreement currently covers a mesenchymal stem cell therapeutic from NantKwest, whose goal is to reduce the time a critically ill patient spends on a ventilator.

“By working together and combining the novel technologies of the two companies, as well as their resources, we believe we have been able to more rapidly develop products that will address the needs of COVID-19 patients,” said Soon-Shiong, who also serves as Chairman and CEO of NantKwest.