BARDA-sponsored study shows second-generation hAd5 vaccine candidate in both subcutaneous and room temperature oral formulations inhibits SARS-CoV-2 virus replication to undetectable levels and clears infection within days in 100% of vaccinated non-human primates
- The second-generation human adenovirus vector hAd5, which delivers both outer spike (S) and inner nucleocapsid (N) antigens, induced T cells and antibodies leading to reduction of SARS-CoV-2 viruses in both lungs and nasal passages within seven days
- The hAd5-COVID-19 oral capsule vaccine candidate was effective at room temperature in non-human primates suggesting that it may not require cold chain logistics that can impede global distribution
- The hAd5-COVID-19 oral vaccine candidate will enter Phase 1 human trials as a prime and a boost and, pending discussions with the FDA, will be explored to provide a boost to subcutaneous vaccinations
- Twenty participants have completed testing in the Phase 1 trial at Hoag Hospital Newport Beach, Calif., which evaluated both low and high doses of subcutaneous hAd5, with zero grade 3/4 adverse events reported. The Phase 2 trial is now actively recruiting.
CULVER CITY, Calif., December 10, 2020 – ImmunityBio, a privately-held immunotherapy company, today announced its COVID-19 vaccine candidate protected nasal and lung airways of non-human primates against coronavirus (SARS-CoV-2) in a challenge study. The study, sponsored by the Biomedical Advanced Research & Development Authority (BARDA), provides further evidence supporting the company’s use of a second-generation adenoviral vector that induces the immune system to both activate T cells and generate antibodies against multiple viral targets—blocking virus replication and clearing existing infection.
In the study, immunization with the hAd5-COVID-19 vaccine inhibited SARS-CoV-2 virus replication in 100% (10 of 10) of Rhesus macaques, with a drop in viral replication starting on the first day of vaccine administration, and undetectable viral levels as early as three to five days post-challenge in most of the animals. The vaccine targeted both the inner nucleocapsid (N) and the outer spike (S) proteins of the virus to maximize the immune response. The goal of targeting both S and N was to both activate virus-specific T cells and generate anti-SARS-CoV-2-neutralizing antibodies. The study showed this broad immune response led to the complete clearance of the virus in a matter of days after infection of previously-vaccinated primates. This blocking of viral replication was observed in both the lung and nasal passages. By protecting the nasal passages (the primary point of entry for the virus), the vaccine has the potential to reduce reinfection. Clearing replicating viruses from nasal passages is critical for reducing transmission of the virus from immunized recipients to others.
The hAd5-COVID-19 candidate is designed to address a potential problem that may emerge when first-generation adenoviral platforms are used as vaccine vectors: vaccine inactivation due to pre-existing immunity to the vector itself. This risk exists for many vaccine candidates being tested in Europe, China, Russia, and the United States. Many people who have been exposed to the “common cold” potentially develop adenovirus immunity: the immune system often attacks and disables these first-generation vaccines before they can activate the immune response to attack the SARS-CoV-2 virus. This can significantly limit the effectiveness of first-generation platforms. ImmunityBio has engineered the vector to overcome this problem and has shown that its second-generation adenovirus vector can safely and effectively deliver its cargo even in patients with pre-existing adenovirus immunity.1.
“These results provide compelling evidence of the need for vaccines to target both S and N proteins and to activate T cells to produce immune system memory to combat this virus,” said Patrick Soon-Shiong, MD, Chairman and CEO of ImmunityBio. “The adage that ‘B cells forget but T cells remember’ has never been more important, and leveraging the S plus N combination has resulted in a vaccine that is not only showing evidence of being effective but also one that has the potential to provide long-term T-cell memory. The exciting finding that the thermally-stable oral formulation triggers immune responses sufficient to inhibit virus replication to undetectable levels bodes well for the possibility that this oral formulation could serve as a universal heterologous booster. Our oral capsule could be a solution to the enormous challenges facing cold chain logistics and enable global distribution of the vaccine.”
The manuscript detailing these preclinical data is available on a preprint server at https://biorxiv.org/cgi/content/short/2020.12.08.416297v1 and is concurrently undergoing scientific peer-review for potential publication.
In vivo Non-Human Primate (NHP) Challenge Study Design
This study was designed to test the safety, immunogenicity and protection from infection and disease provided by ImmunityBio’s hAd5-COVID-19 vaccine. The vaccine was administered in two separate regimens. In the first, primates received subcutaneous (SC) vaccination on Day 0, followed by an SC boost on Day 14 and an oral boost on Day 28. In the second, the SC prime was followed by two oral boosts on the same schedule. Placebo controls were used for comparison for both. Subcutaneous injection of hAd5 and oral administration of enteric-coated capsules in Rhesus macaques did not result in any treatment-related toxicities.
- ImmunityBio’s hAd5-COVID-19 vaccine was determined to be well tolerated following both subcutaneous and oral capsule administration.
- ImmunityBio’s hAd5 vaccine activated T cells to provide protection, and N was particularly effective in this role. This feature of the hAd5 vaccine distinguishes it from other vaccines.
- ImmunityBio’s hAd5 vaccine generated robust neutralizing antibody activity that was present 14 days post-final vaccination. Additional safety and neutralizing data are currently being collected/analyzed.
- Both vaccination regimens resulted in complete protection from subsequent viral ‘challenge’ as reflected by reductions in viral RNA levels that were below the level of detection by day seven post-challenge compared to controls.
hAd5-COVID-19 Oral Formulation
The hAd5-COVID-19 liquid drug substance was dried (lyophilized) and encapsulated to create the thermally-stable oral version of the vaccine. The capsules are enterically-coated to allow passage through the stomach to the small intestine, where the capsule dissolves to deliver the vaccine. Pending discussions with the FDA, the oral vaccine will enter Phase I trials as a prime and boost, and will be explored to provide a boost to subcutaneous vaccinations.
For more information about ImmunityBio’s COVID-19 vaccine trials, please contact firstname.lastname@example.org.
About ImmunityBio and NantKwest Joint Collaboration Agreement
Under the terms of a definitive agreement announced on August 24, 2020, ImmunityBio, Inc. and its affiliate NantKwest, Inc. 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.
ImmunityBio, Inc. is a 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.” 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 human adenovirus (hAd5) vaccine technologies.
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 is also in Phase 2 or 3 trials for indications such as 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 (hAd5) vaccine technologies.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements concerning or implying that ImmunityBio will be successful in improving the treatment of the novel coronavirus, the timing and results of the clinical development of had5-COVID -19 oral capsule vaccine, or whether ImmunityBio will be successful in gaining regulatory approval of, commercializing or distributing the vaccine. Risks and uncertainties related to these endeavors include, but are not limited to the successful completion of the currently contemplated Phase 1 trials and the currently enrolling Phase 2 trial and subsequent clinical development and FDA approval of the vaccine on the currently anticipated timeline, if at all, as well as manufacturing and distribution challenges., Risks and uncertainties related to this endeavor include, but are not limited to, the company’s beliefs regarding the success, cost, and timing of its development activities and clinical trials.
Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.
NantKwest (NASDAQ: NK) is an innovative, clinical-stage immunotherapy company focused on harnessing the power of the innate immune system to treat cancer and infectious diseases. NantKwest is the leading producer of clinical dose forms of off-the-shelf natural killer (NK) cell therapies. The activated NK cell platform is designed to destroy cancer and virally-infected cells. The safety of these optimized, activated NK cells—as well as their activity against a broad range of cancers—has been tested in phase I clinical trials in Canada and Europe, as well as in multiple phase I and II clinical trials in the United States. By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs, NantKwest’s goal is to transform medicine by bringing novel NK cell-based therapies to routine clinical care. NantKwest is a member of the NantWorks ecosystem of companies. For more information, please visit www.nantkwest.com
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements concerning or implying that NantKwest will be successful in improving the treatment of cancer or other critical illnesses, including COVID-19. Risks and uncertainties related to these endeavors include, but are not limited to, obtaining FDA approval of NantKwest’s NK cells and MSC as well as other therapeutics and manufacturing challenges.
Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements.
These and other risks regarding NantKwest’s business are described in detail in its Securities and Exchange Commission filings, including in NantKwest’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2020. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update these statements except as may be required by law.