4 August 2020 - - US-based immunotherapy company ImmunityBio, Inc has received positive preclinical results for its human Ad5 vaccine candidate that contains both the spike (S) and nucleocapsid (N) SARS-CoV-2 proteins (hAd5 S + N) for preventing COVID-19, the company said.

The results were published in bioRxiv ("A Next Generation Bivalent Human Ad5 COVID-19 Vaccine Delivering Both Spike and Nucleocapsid Antigens Elicits Th1 Dominant CD4+, CD8+ T Cell and Neutralizing Antibody Responses").

First generation adenoviral-based vaccines are hampered by pre-existing adenovirus immunity, which reduces the immunogenicity of the vaccines.

In addition, with vaccines that target S alone, there is a risk that they may be rendered ineffective due to the high likelihood of spike protein mutation.

The preclinical study showed that the bivalent hAd5 vaccine resulted in robust T cell and humoral immune responses against SARS-CoV-2 S and N antigens. Immunogenicity in mice was assessed after two doses given 21 days apart (Day 0 and Day 21).

Immune responses measured on Day 28 showed that the vaccinations elicited robust T cell responses to SARS-CoV-2. Importantly, a statistically significant CD4+ T cell response to N protein was generated in all five mice.

This is consistent with studies in patients who have recovered from SARS-CoV who show memory T cells to N protein.

Four out of 5 mice generated an S-specific antibody response, with evidence of Th1 dominance. Two of these mice demonstrated potent neutralizing antibodies as they relate to the RBD ACE2 interface.

Analysis of both T cell cytokine responses and antibody isotypes demonstrated that the overall immune response was highly skewed towards T helper cell dominance important for mitigating the risk of antibody-dependent enhancement of infection.

ImmunityBio plans to administer the hAd5 vaccine both as a prime and a booster to sustain protection against SARS-CoV-2. The company has completed GMP dosage formulations that have already been manufactured in the United States.

In ongoing studies, use of this vaccine construct in oral and sublingual formulations to induce mucosal, cell-mediated, and humoral immunity are being explored.

ImmunityBio has filed an Investigational New Drug application with the FDA to initiate Phase 1 trials of this next-generation hAd5 S+N vaccine to be administered subcutaneously in healthy volunteers.

The company plans to submit the full data from this study for publication in a peer-reviewed journal in the coming weeks.

Agreement to Jointly Develop, Manufacture and Market COVID-19 Therapeutics and Vaccine

In May, NantKwest and ImmunityBio entered into a binding term sheet to pursue collaborative joint development, manufacturing, and marketing of certain COVID-19 therapeutics and vaccines.

The parties intend to equally share all costs relating to developing, manufacturing and marketing the product candidates globally; the net profits from the collaboration products will be shared, with 60% in favor of the party contributing the product on which the sales are based.

The companies are negotiating the terms of a definitive agreement and anticipate finalizing documentation before August 21, 2020 after which either party can terminate the binding term sheet upon five business days' written notice if an agreement is not finalised.

ImmunityBio is a late-stage immunotherapy company developing next-generation therapies that drive immunogenic mechanisms for defeating cancers and infectious disease.

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."

This novel approach is designed to eliminate the need for high-dose chemotherapy, improve upon the outcomes of current CAR T-cell therapies, and extend beyond checkpoint inhibitors.

ImmunityBio's platform is based on the foundation of three separate modalities: antibody cytokine fusion proteins, synthetic immunomodulators, and second-generation vaccine vector technologies.

ImmunityBio's lead cytokine infusion protein, a novel interleukin-15 (IL-15) superagonist complex (Anktiva), has received Breakthrough Therapy and Fast Track Designations from the US Food and Drug Administration for BCG-unresponsive CIS non-muscle invasive bladder cancer (NMIBC).

Other indications currently at registration-stage trials include BCG-unresponsive papillary bladder cancer, first and second line lung cancer, triple-negative breast cancer, metastatic pancreatic cancer, recurrent glioblastoma, and soft tissue sarcoma in combination with the company's synthetic immune modulator (Aldoxorubicin).

ImmunityBio is also developing therapies, including vaccines, for the prevention and treatment of HIV, influenza, and the coronavirus SARS-CoV-2 with its second-generation human adenovirus vaccine platform.

NantKwest (NASDAQ: NK) is a clinical-stage immunotherapy company focused on harnessing the power of the innate immune system to treat cancer and virally-induced infectious diseases.

NantKwest is a producer of clinical dose forms of off-the-shelf natural killer cell therapies. The activated NK cell platform is designed to destroy cancer and virally-infected cells.