ImmunityBio Announces Novel ACE2 Decoy COVID-19 Therapeutic that Shows High Binding to SARS-CoV-2 Variants and Neutralizes Live Viruses

The hAd5 ACE2 Decoy candidate is based on modified ACE2 receptors that would compete with ACE2 on the cells of respiratory tract for binding of the SARS-CoV-2 virus. The ACE2 Decoy would trap the virus, preventing it from infecting cells and facilitate clearance of the virus from the body. ImmunityBio’s advanced molecular dynamic simulation capability previously reported in December was leveraged to design the ACE2 Decoy so it would have higher affinity for the virus, including SARS-CoV-2 variants, than natural ACE2 found on cells.

“The rapid mutation of the SARS-CoV-2 virus, predominantly in the structure of the spike protein, and the emergence of variants over-taking the ‘first wave’ virus poses a real threat to our ability to end the pandemic,” said Patrick Soon-Shiong, M.D., Executive Chairman of ImmunityBio. “Our goal is to outsmart these variants by trapping them with decoy versions of the ACE2 receptor, and the findings we presented at CROI show our lead ACE2 Decoy binds with even greater affinity to the concerning viral variants with E484K and N501Y mutations. These promising results warrants our decision to advance a second hAd5 therapeutic vaccine into clinical development.”

hAd5 ACE2 Decoy Therapeutic

The CROI presentation, titled “A SARS-CoV-2 Neutralizing ACE2 Decoy Shows High Affinity for N501Y and L452R Variants,” highlighted ImmunityBio’s development of a recombinant protein construct designed to act as a ‘decoy’ human angiotensin converting enzyme 2 (ACE2) receptor that would compete with ACE2 on cells of the respiratory tract to bind the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. An effective, high-affinity decoy could potentially be used as a COVID-19 therapeutic by out-competing human ACE2 receptors for binding to SARS-CoV-2 S RBD, thereby inhibiting infection events in vivo. It also has the potential to be used as a prophylactic that might be administered to individuals at high risk for infection as a complement to vaccination to assure protection.

Given the recent emergence and rapid spread of COVID-19 cases due to several SARS-CoV-2 variants with mutations in the S RBD, including variants originating in the United Kingdom, South Africa and California, ImmunityBio scientists sought to identify a single ACE2 decoy candidate with robust binding affinity across wild-type and variant SARS-CoV-2 S RBDs, which might thus demonstrate efficacy in neutralizing infection with SARS-CoV-2 of any known genotype.

The ACE2 Decoy not only maintains its high affinity for S RBD expressing these mutations, but shows enhanced affinity for S RBD expressing the N501Y or L452R mutations and the highest affinity for S RBD expressing both the E484K and N501Y mutations. The candidate warrants continued development, beginning with testing in challenge studies.

About ImmunityBio

ImmunityBio is a leading late-clinical-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious diseases. The company’s immunotherapy platform activates both the innate (natural killer cell and macrophage) and adaptive (T cell) immune systems to create long-term “immunological memory.”

ImmunityBio has an unparalleled immunotherapy pipeline with more than 40 clinical trials (company sponsored or investigator initiated)—of which 25 are at Phase II and III stage of development—across 19 indications in solid and liquid cancers and infectious diseases. Currently 17 first-in human immunotherapy agents are in clinical testing and, to date, over 1,800 patients have been studied with our antibody cytokine fusion proteins, albumin chemo immunomodulators, Adeno and yeast vaccines and our off-the-shelf natural killer cell products. Anktiva™ (ImmunityBio’s lead cytokine infusion protein) is a novel interleukin-15 (IL-15) superagonist complex and has received Breakthrough Therapy and Fast Track Designations from the U.S. Food and Drug Administration (FDA) for BCG-unresponsive CIS non-muscle invasive bladder cancer (NMIBC).

The company’s platforms are based on the foundation of four separate modalities: Antibody cytokine fusion proteins, synthetic immunomodulators, second-generation human adenovirus (hAd5) and yeast vaccine technologies, and state-of-the-art, off-the-shelf natural killer cells, including autologous and allogenic cytokine-enhanced memory NK cells.

ImmunityBio is a leading producer of cryopreserved and clinical dose forms of off-the-shelf natural killer (NK) cell therapies. The company has established GMP manufacturing capacity at scale with cutting-edge cell manufacturing expertise and ready-to-scale facilities, as well as extensive and seasoned R&D, clinical trial, and regulatory operations and development teams. For more information, please visit: www.immunitybio.com

Forward Looking Statements

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