Benzinga | Jan 19, 2021 08:10AM EST

NantKwest M&A Partner ImmunityBio Announces Phase I Trial Of COVID-19 Vaccine Candidate

Plans to study COVID-19 subcutaneous and oral, room-temperature capsule vaccine to protect against escape mutants

* ImmunityBio to conduct initial trial of its human adenovirus (hAd5) COVID-19 vaccine candidate in South Africa, where the 501Y.V2 strain has been recently identified

* Recent computer modeling by ImmunityBio revealed that an E484K mutation when combined with the N501Y (UK mutation) resulted in conformational changes in the South African 501Y.V2 virus strain, which may lead to resistance to antibodies and convalescent serum

* ImmunityBio's vaccine candidate--in subcutaneous, oral and sublingual formulations--activates virus-specific T-cells and generates memory B cells with neutralizing antibodies, which may potentially protect against emerging SARS-CoV-2 antibody resistant mutations

* ImmunityBio's vaccine has shown evidence of protection after subcutaneous and oral administration in non-human primates challenged with SARS-CoV-2

* Unlike other adenovirus-based COVID-19 vaccine candidates, ImmunityBio's uses a second-generation Ad5 platform designed to raise anti-SARS-CoV-2 immune responses even in Ad-immune individuals, meaning subjects can receive the vaccine multiple times, if necessary

* Phase I trial recruitment is set to begin in February in Cape Town, South Africa with subcutaneous doses to be followed by trials using sublingual doses and room temperature-stable oral capsules

ImmunityBio, Inc., a privately-held immunotherapy company, today announced it has received authorization from the South Africa Health Products Regulatory Authority (SAHPRA) to begin a Phase I clinical trial of its hAd5 T-cell vaccine, the company's novel COVID-19 vaccine candidate, which will be administered subcutaneously. The same vaccine is currently being tested in a similar Phase I trial in the U.S., with no safety concerns identified to date. With the goal of creating longer-term protection from the virus, hAd5-COVID-19 targets both the mutation-prone outer spike protein (S) and the more stable inner nucleocapsid (N) protein, activating antibodies, memory B cells, and T-cells against the coronavirus (SARS-CoV-2).

This novel vaccine candidate is delivered subcutaneously and via a room-temperature oral capsule formulation and has the potential to serve as a universal T-cell boost to current vaccines or address mutations where other vaccines might fail, including the 501Y.V2 variant, which has been found in patients in South Africa. This increases the urgency that a range of COVID-19 vaccines be available to the global population where mutations are rapidly occurring.

Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio stated, "We are excited about the potential of our COVID-19 vaccine candidate and the issues it could solve globally. Unlike antibody-based vaccines, T-cell-based vaccines kill the infected cell, preventing virus replication, and could provide long-term immune memory to recipients. Pursuing a vaccine that does not rely solely on targeting the S protein where the mutations are occurring is of critical importance as multiple variants of the SARS-CoV-2 virus have appeared globally, with concentrated outbreaks beginning in South Africa."

Dr. Soon-Shiong continued, "After leveraging this concept in our novel COVID-19 oral vaccines, we saw complete protection to a viral challenge in our non-human primate data. These exciting results have catalyzed our interest in pursuing human trials of the oral vaccine in South Africa. We believe this T-cell vaccine approach to mutational changes could also be explored for other infectious diseases such as influenza, potentially obviating the need for annual injections."

Prof. Tulio de Oliveira, a professor and geneticist at the Nelson Mandela School of Medicine in Durban, said, "Our scientists at the University of KwaZulu-Natal have discovered that patients who recovered from the first wave of COVID-19 may no longer be protected from the new local SARS-CoV-2 variants. These mutations are now rapidly spreading through the rest of Africa and the world. We are hopeful that by teaming up with ImmunityBio, the now rampant 501Y.V2 variant in our country can soon be eliminated and protected against for good. We are excited to be working with the scientific team at ImmunityBio to study the effects of a T-cell vaccine in patients infected with the 501Y.V2 variant now rampant in our country."

Prof. Tulio de Oliveira, a professor and geneticist at the Nelson Mandela School of Medicine in Durban, "Our scientists at the Network for Genomic Surveillance in South Africa (NGS-SA) have discovered that the 501Y.V2 spread much faster than previous variants in South Africa. We are also finding that patients who recovered from the first wave of COVID-19 may no longer be protected from the new local SARS-CoV-2 variants. These mutations are now rapidly spreading through the rest of Africa and the world. We are hopeful that by teaming up with ImmunityBio, the now rampant 501Y.V2 variant in our country can soon be eliminated and protected against for good. We are excited to be working with the scientific team at ImmunityBio to study the effects of a T-cell vaccine in patients infected with the 501Y.V2 variant now rampant in our country."

"I'm pleased to study this next-generation adenovirus vaccine platform for COVID-19 at the University of Cape Town. This is the third adenovirus-based COVID-19 vaccine to enter trials in South Africa. Understanding sensitivities related to adeno vaccine platforms in South Africa, we have taken the utmost care in designing our trial," said Dr. Amy Ward, principal investigator of the Phase I trial.

"This Phase I trial and the planned development strategy for this vaccine are critical for us in South Africa towards addressing the health and social crisis that COVID-19 has caused in our country and the threat posed by the spread of new variants. The possibility of oral capsules for boosting doses is very exciting. ImmunityBio has engaged with government agencies and indicated a commitment to ensuring this vaccine is available in South Africa. Hence, the importance that we evaluate it here from Phase I trials onwards" said Dr. Graeme Meintjes, Professor and Second Chair in the Department of Medicine at the University of Cape Town and a co-investigator on the trial.

About the T-Cell-Based Vaccine Candidate

Developed by ImmunityBio and manufactured by NantKwest, Inc. (NASDAQ:NK), this second generation hAd5-vector vaccine is unique in targeting both spike (S) and nucleocapsid (N) SARS-CoV-2 proteins potentially generating B and T cell memory to the COVID-19 antigens and long-term immunity to the virus. Most of the COVID-19 vaccines approved by the FDA or in late-stage clinical trials deliver only the spike protein on the surface of the virus, which has already mutated several times. Another unique characteristic of the hAd5 design is it uses a second-generation Ad5 platform that was developed to raise anti-SARS-CoV-2 immune responses even in Ad-immune individuals, meaning subjects can receive the vaccine multiple times, if necessary. The stimulation of anti-Ad5 immune responses is attenuated with the second-generation platform in comparison with the first-generation platforms, due to additional genetic deletions. Phase I trials have been initiated in the U.S. and recruitment is set to begin in February in Cape Town, South Africa with subcutaneous doses to be followed by trials using sublingual doses and room temperature-stable oral capsules.

Joint Collaboration Agreement with NantKwest

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 commercialization of the products each is developing related to COVID-19, including the hAd5 vaccine candidate. Should a product be commercialized successfully, the companies have agreed to a 60-40 percent split of net profits, with the larger share going to the company that developed the product. The agreement also details the structure of shared governance of the joint collaboration.

NantKwest Transaction

As previously announced, on December 21, 2020, ImmunityBio entered into an agreement to combine in a stock-for-stock transaction with NantKwest. The combination, which is expected to close in the first half of 2021, will create a leading immunotherapy and cell therapy company focused on oncology and infectious disease.