EL SEGUNDO, Calif., May 27, 2020 – NantKwest, Inc. (Nasdaq: NK), a clinical-stage, natural killer cell-based therapeutics company, and ImmunityBio, a privately-held immunotherapy company, today announced ImmunityBio has been selected to participate in Operation Warp Speed, a new national program aiming to provide substantial quantities of safe, effective vaccine for Americans by January 2021. Efforts will focus on the development, testing, and large-scale manufacturing of ImmunityBio’s COVID-19 human adenovirus vaccine (hAd5) candidate. This is the first vaccine designed to deliver both Spike (S) and Nucleocapsid (N) DNA, offering the potential for patients to develop long-lasting immunity to the virus.

This novel, E1, E2b, E3 deleted, human adenovirus vector has demonstrated safety in over 125 patients in 13 Phase 1 and 2 trials to date. Clinical studies performed by the National Cancer Institute have demonstrated that this novel Ad5 may induce antigen-specific T-cell immunity in patients, even in the presence of pre-existing adenoviral immunity.

The companies also announced that the U.S. Food and Drug Administration (FDA) has authorized the use of ImmunityBio’s IL-15 (generic name nogapendekin alfa inbakicept) to treat patients prior to the onset of severe disease by potentially activating natural killer cells to mitigate viral replication. On May 18, NantKwest announced FDA authorization to study the use of mesenchymal stem cell treatments to modulate the immune system’s excessive response to COVID-19 infection, thereby potentially reducing the debilitating and sometimes fatal effects of the disease.

To support these coordinated efforts from vaccine to therapeutics, the two companies have signed a binding term sheet to jointly develop, manufacture, and market therapeutics and vaccines for COVID-19. The binding agreement outlines how development costs will be shared, how profits will be apportioned for any successfully marketed products, and the structure of shared governance of the joint work.

“ImmunityBio is honored to have been selected as one of the 14 companies for Operation Warp Speed and is committed to moving our vaccine candidate through the process to prevent people from contracting this deadly virus,” said Patrick Soon-Shiong, M.D., Chairman and CEO of ImmunityBio and NantKwest. “Using our unique technologies, we are working just as furiously to develop therapeutics for people who are already infected. With this work, we hope to contain and eventually conquer the virus.”

Covid-19 Vaccine: Immunologically “Stealth” Ad5 platform uses E1, E2B, E3 deleted human adenovirus to deliver unique N+S COVID construct with potential for DNA transcription for months leading to long term cell-mediated immunity

ImmunityBio’s COVID-19 vaccine candidate is a novel, engineered Ad5 vaccine (as compared to the one based on the chimpanzee adenovirus currently in COVID-19 vaccine trials in Europe, or the first-generation human adenovirus in trials in China), and the first COVID-19 vaccine designed to deliver both Spike (S) and Nucleocapsid (N) DNA, which offers the potential for patients to develop long-lasting immunity to the virus.

This human adenovirus platform represents an improvement over first-generation adeno-associated virus vectors, which produce large amounts of adenoviral fiber, which leads to high levels of adenoviral-neutralizing antibodies that, in turn, diminish the ability for the vaccine to be produced in the patient and thus limit ongoing immune response. In addition, the absence of the production of these adenoviral neutralizing antibodies enables this second-generation adenovirus to be administered as a prime and boost (homologous vaccination).

The vaccine is based on a human adeno virus platform, engineered to prevent the generation of adenoviral proteins with the objective that they remain “stealth” after being injected. This potentially allows long-term production of the vaccine construct in the body, even in the presence of pre-existing neutralizing antibodies. With this unique property of being “immunologically silent” in the human body, the vaccine may produce the vaccine blueprint signal for months, thus maximizing the opportunity to establish long term immunity and potential T-cell memory. This Ad5 platform has already demonstrated safety in elderly and immuno- suppressed patients in the oncology setting.  Large- scale manufacturing facilities at NantKwest have been activated, with an expectation of delivering an Ad5 vaccine in high volumes later this year.

• ImmunityBio’s Ad5 platform is designed to be “immunologically stealth,” enabling the DNA delivered by this “quiet” adenovirus system to continuously produce its vaccine antigen for potentially over four months. This is in sharp contrast to mRNA vaccines, which can only survive a few days in-vivo.
• In multiple clinical studies in patients with advanced cancer, this second-generation Ad5 platform showed immune response even in the face of adenoviral-neutralizing antibodies. Overcoming this immune resistance made multiple re-dosing possible.
• A track record of preliminary safety of high doses (up to 15 times the anticipated COVID-19 vaccine dose) has been shown in Phase I and Phase II studies in immunosuppressed cancer patients.
• The IND has been filed with the FDA and clinical trials are anticipated to begin in June.
• Two GMP-ready manufacturing plants have been readied for COVID-19 vaccine production with capacity for 100 million doses by year-end.

COVID-19 therapeutics address the evolving stages of disease, from moderate infection to severe acute respiratory distress syndrome (SARS) 

• Therapeutic immunomodulators for patients with mild-to-moderate COVID-19 symptoms:
  • ImmunityBio’s N-803: Interleukin 15 (IL-15) ‘superagonist’ cytokine (Nogapendekin alfa inbakicept) to stimulate natural killer cells and CD8+ T-cells; FDA IND authorization received (NCT 04385849).
  • Highly selective Interleukin 15 ‘superagonist’ N-803, which has higher activity and is longer lasting than native IL-15, and has the potential to overcome low natural killer cell and T-cell count in patients with COVID-19 infections.
  • A randomized, blind, placebo-controlled Phase 1b trial will assess N-803’s safety and immunostimulatory activity in COVID-19. Thirty subjects who have tested positive for SARS-CoV-2 and have confirmed mild-to-moderate COVID-19 symptoms will be enrolled.
  • Phase 1 trials expected to begin in Los Angeles area hospitals in June 2020.
  • NantKwest’s haNK: CD-16, off-the-shelf natural killer cellsto enhance antibody killing of infected cells, given alone or combined with Convalescent Plasma (CP); Pre-IND has been submitted to the FDA.
• Therapeutic for severe and critically ill COVID-19 patients on ventilator support:
  • NantKwest’s MSCs: Bone marrow-derived mesenchymal stem cells (MSC) to mitigate ‘cytopathic storm’; FDA authorization received (NCT 04397796).
  • Announced on May 18, 2020, the Phase 1b, randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of BM-Allo.MSC versus current supporting care in treating patients with severe disease requiring ventilator support. The therapeutic will be administered to 45 patients in critical care or an ICU setting. The primary objectives of the study include overall safety, and reduced time on a ventilator. The secondary objective is the efficacy of BM-Allo.MSC in reducing the number of days patients require oxygen, duration of hospitalization, and mortality.
  • Trials to begin in early June 2020 in the Los Angeles area.

“While we urgently research vaccines for COVID-19, we need to find effective therapeutics for treating all stages of the infection, which places divergent pressures on the immune system at different stages,” said Dr. Soon-Shiong. “Based on initial data, we believe our IL-15 superagonist N-803 could prevent patients from reaching the most advanced stages of disease, including pneumonia and acute respiratory distress syndrome (ARDS). Our goal is to reduce the severity of infection and the number of COVID-19 patients requiring hospitalization.”

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

On May 22, 2020, 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 agree to jointly develop haNK, mesenchymal stem cells (MSC), adenovirus constructs (Ad5), and N-803 for the prevention and treatment of SAR-CoV-2 viral infections and associated conditions, including COVID-19.  NantKwest will contribute the haNK, MSC, and certain of its manufacturing capabilities, and ImmunityBio will contribute Ad5, IL-15, and certain manufacturing equipment.

Under the terms of the agreement, the parties will share equally in all costs relating to developing, manufacturing, and marketing of the product candidates globally, and the global net profits from the collaboration products will be shared 60%/40% in favor of the party contributing the product on which the sales are based.  All net profits from sales of combined collaboration products will be shared equally. This collaboration will be supervised by joint committees, comprised of an equal number of representatives from both companies.

NantKwest and ImmunityBio will be hosting a call for institutional investors, sell-side analysts, and business development professionals on Wednesday, May 27 at noon EDT to discuss the companies’ COVID-19 therapeutic and vaccine initiatives. A link to register for the event can be found here and on the companies’ websites, Nantkwest.com and ImmunityBio.com. The presentation will be available on the websites following the call.

About NantKwest

NantKwest (NASDAQ: NK) is an innovative, clinical-stage immunotherapy company focused on harnessing the power of the innate immune system to treat cancer and virally-induced 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 delivering off-the-shelf, 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.

haNK is a registered trademark of NantKwest, Inc.

About ImmunityBio

ImmunityBio, Inc. is a privately-held immunotherapy company with a broad portfolio of biological molecules at clinical stages of development. The company’s goals are to employ this portfolio to activate endogenous natural killer and CD8+ T-cells in the fields of cancer and infectious disease. Specifically, ImmunityBio’s goal is to develop a memory T-cell cancer vaccine to combat multiple tumor types—without the use of high-dose chemotherapy. Regarding infectious disease, ImmunityBio is addressing HIV, influenza, and coronavirus.

ImmunityBio’s first-in-human platform of technologies has enabled it to achieve one of the most comprehensive, late-stage clinical pipelines, activating both the innate (natural killer cell) and adaptive immune systems. The product pipeline includes an albumin-linked chemotherapeutic (Aldoxorubicin), a novel IL-15 cytokine superagonist (N-803), checkpoint inhibitors, macrophage polarizing peptides, bi-specific fusion proteins targeting TGFb and IL-12, adenovirus, and yeast vaccine therapies targeting tumor-associated antigens and neoepitopes.

In December 2019, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to N-803 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, and metastatic pancreatic cancer.

ImmunityBio’s goal is to develop therapies, including vaccines, for the prevention and treatment of cancer, HIV, influenza, and the coronavirus SARS-CoV-2.

Source: ImmunityBio, Inc.

Posted: May 2020