ImmunityBio and NantKwest Announce FDA Authorization to Study hAd5 T-Cell COVID- 19 Vaccine for Combination of Subcutaneous, Oral and Sublingual Boost to Induce T- Cell, Mucosal, and Antibody Immunity
- FDA authorized the expansion of the active Phase 1 COVID-19 vaccine trial and a second trial to test a novel combination of T-cell-based hAd5 subcutaneous prime vaccine with a room- temperature oral or sublingual boost, to induce comprehensive immune protection through
CD4+ and CD8+ T cells to both Spike (S) and Nucleocapsid (N) antigens, as well as generate systemic and mucosal antibodies
- The first COVID-19 trials conducted to deliver both S and N proteins via multiple routes (skin, gut, or under the tongue) to activate the entire immune system and drive T-cell and B-cell memory, which are required for long-term immune protection
- Oral, room-temperature boost that stimulates immunity to both S and N proteins could potentially serve as a universal boost to other S-based vaccines while also targeting escape mutants
- Testing of novel combination of oral boost to subcutaneous prime is based on positive NIH/BARDA-sponsored non-human primate data showing potent T-cell and antibody response to hAd5 after oral boost, with rapid inhibition of virus replication to undetectable levels following SARS-CoV-2 challengeCULVER CITY, Calif., February 11, 2021 – ImmunityBio, Inc., a privately-held immunotherapy company, and NantKwest, Inc. (NASDAQ: NK), a clinical-stage, natural killer cell-based therapeutics company, today announced they have received FDA authorization to expand Phase I testing of a bivalent hAd5 T-cell COVID-19 vaccine. The FDA authorized the expansion of a currently active multi- cohort trial of the subcutaneous version of the vaccine in order to study the addition of sublingual boosts. The FDA also authorized a second Phase I study that will examine the addition of an oral boost to the subcutaneous prime administration. As a result, the companies will enroll another 105 participants in the U.S. trials of their vaccine candidate, which is unique in targeting both the spike (S) and nucleocapsid (N) proteins of the SARS-CoV-2 virus.The expectations of inducing protective immune responses in healthy volunteers – with this novel combination of an oral boost with a subcutaneous prime – are based on the positive findings reported in the NIH/BARDA-sponsored Non-Human Primate (NHP) study. This recent data showed that when administered with an oral boost, the bivalent vaccine resulted in potent stimulation of S- and N-specific T cells with potent antibody release from memory B cells following viral challenge. Additionally, activation of the full immune system by S and N proteins resulted in complete viral clearance of SARS- CoV-2 in lung and nasal passages following the challenge. On the basis of these findings, ImmunityBio has expanded the current Phase 1 study of subcutaneous prime with oral or sublingual boost to explore the potential of this second-generation vaccine to reduce disease and transmission of the virus.
The oral trial is a new study (NCT04732468) and the sublingual trial is the cohort C expansion to the Phase 1 subcutaneous trial (NCT04591717), which was initiated last Fall. Both oral and sublingual trials are anticipated to begin this month and will be conducted at two sites in California. Based on the findings of these trials involving over 100 participants, the optimal combination of route of administration and dose will be determined and entered into the Phase 2 / 3 design.
“The NHP study findings reinforce our hypothesis that a T-cell-based vaccine could be protective, not only in preventing mild, moderate, and severe disease, but also in potentially limiting transmission of the virus,” said Patrick Soon-Shiong, MD, Chairman and CEO of ImmunityBio. “We believe that the key to creating long-term immunity to the SARS-CoV-2 virus and overcoming the variants that are rapidly developing around the world is to create a vaccine that activates not only antibodies but also memory B and T cells to multiple antigens. Furthermore, room-temperature stable formulations for oral delivery have the potential to solve the cold-chain challenges of distribution and the ability to generate mucosal IgA antibody barriers to the virus in the upper respiratory tract where it first enters the body.”
One Vaccine, Two Trials, Three Routes of Immune Protection
The first two cohorts of the Phase Ib, open label, dose-ranging study (NCT04591717) of the
vaccine received two different dose levels (.5 and 1ml). Participants received two subcutaneous injections 21 days apart. No grade three or four AEs and no SAEs were observed at either dose level and, in the intermediate (1ml) dose group, immunogenicity was observed as early as 14 days after the prime. An additional group of 40 subjects will be enrolled to evaluate safety, reactogenicity, and immunogenicity of the combination of hAd5 in four different cohorts receiving sublingual and subcutaneous formulations to select an optimal combination dose for future studies.
The second Phase 1b trial (NCT04732468) is designed to assess the safety, reactogenicity, and immunogenicity of the combination of hAd5 in oral capsule and subcutaneous formulations; and to select an optimal combination dose for future studies. Up to 65 subjects will be enrolled in the four- cohort study, which is anticipated to begin in Q1.
About the T-Cell-Based Vaccine Candidate
Developed by ImmunityBio and manufactured by NantKwest, this second generation hAd5
vectored vaccine is unique in targeting both spike (S) and nucleocapsid (N) SARS-CoV-2
proteins to generate B and T cell memory to these 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, which has already mutated several times. Another unique characteristic of the hAd5 design is its use of a second-generation hAd5 platform that was developed to elicit 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-hAd5 immune responses is attenuated with the second-generation platform in comparison with the first-generation platforms, due to additional genetic deletions. The hAd5
room temperature-stable oral capsules were developed in partnership with UK-based biotechnology company iosBio.
Phase I trials have been initiated in the U.S. and recruitment is set to begin in February in Cape Town, South Africa for a trial (NCT04710303) of subcutaneous administration to be followed
by additional trials using sublingual delivery and room temperature-stable oral capsules.
As previously announced, on December 21, 2020, ImmunityBio entered into an agreement to combine in a stock-for-stock transaction with NantKwest (NASDAQ: NK). 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.
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.
AnktivaTM (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.
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 communication contains forward-looking statements relating to the proposed transaction involving NantKwest, Inc. (“NantKwest”) and ImmunityBio, Inc. (“ImmunityBio”), including financial estimates and statements as to the expected timing, completion and effects of the proposed transaction and statements relating to NantKwest and ImmunityBio’s future success in improving the treatment of various diseases and illnesses, including, but not limited to COVID-19 and cancer. Statements in this communication that are not statements of historical fact are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipates,” “believes,” “continues”, “could”, “estimates,” “expects,” “intends,” “may,” “plans,” “potential”, “predicts”, “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. These forward-looking statements are neither forecasts, promises nor guarantees, and are based on the current beliefs of NantKwest’s management and ImmunityBio’s management as well as assumptions made by and information currently available to NantKwest and ImmunityBio. Such statements reflect the current views of NantKwest and ImmunityBio with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about NantKwest and ImmunityBio, including, without limitation, (i) inability to complete the proposed transaction because, among other reasons, conditions to the closing of the proposed transaction may not be satisfied or waived, (ii) uncertainty as to the timing of completion of the proposed transaction, (iii) potential adverse effects or changes to relationships with employees, suppliers or other parties resulting from the announcement or completion of the proposed transaction, (iv) the outcome of any legal proceedings that may be instituted against the parties and others related to the potential transaction between NantKwest and ImmunityBio, (v) possible disruptions from the proposed transaction that could harm NantKwest’s or ImmunityBio’s respective business, including current plans and operations, (vi) unexpected costs, charges or expenses resulting from the proposed transaction, (vii) uncertainty of the expected financial performance of the combined company following completion of the proposed transaction, including the possibility that the expected synergies and value creation from the proposed transaction will not be realized or will not be realized within the expected time period, (viii) the ability of each of NantKwest or ImmunityBio to continue its planned preclinical and clinical development of its respective development programs, and the timing and success of any such continued preclinical and clinical development and planned regulatory submissions, (ix)
inability to retain and hire key personnel, and (x) the unknown future impact of the COVID-19 pandemic delay on certain clinical trial milestones and/or NantKwest’s or ImmunityBio’s operations or operating expenses. More details about these and other risks that may impact NantKwest’s business are described under the heading “Risk Factors” in NantKwest’s most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (“SEC”) and in subsequent filings made by NantKwest with the SEC, which are available on the SEC’s website at www.sec.gov. NantKwest and ImmunityBio caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. NantKwest and ImmunityBio do not undertake any duty to update any forward-looking statement or other information in this communication, except to the extent required by law. No representation is made as to the safety or effectiveness of these product candidates for the therapeutic use for which such product candidates are being studied.
Certain information contained in this communication relates to or is based on studies, publications, surveys and other data obtained from third-party sources and NantKwest’s and ImmunityBio’s own internal estimates and research. While NantKwest and ImmunityBio believe these third-party sources to be reliable as of the date of this communication, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this communication involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while NantKwest and ImmunityBio each believes its own internal research is reliable, such research has not verified by any independent source.
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Additional Information and Where to Find It
In connection with the proposed transaction, NantKwest filed with the SEC a registration statement on Form S-4, which included a prospectus and joint proxy / solicitation statement of NantKwest and ImmunityBio (the “solicitation statement/prospectus”). The registration statement was declared effective on February 1, 2021 and the solicitation statement/prospectus was first mailed to stockholders of NantKwest on or about February 5, 2021. NantKwest may also file other documents regarding the proposed transaction with the SEC. This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval. This communication is not intended to be, and is not, a substitute for such filings or for any other document that NantKwest may file with the SEC in connection with the proposed transaction. BEFORE MAKING ANY VOTING OR
INVESTMENT DECISION, INVESTORS AND SECURITY HOLDERS ARE URGED TO CAREFULLY READ THE ENTIRE REGISTRATION STATEMENT AND SOLICITATION STATEMENT / PROSPECTUS, AND ANY OTHER RELEVANT DOCUMENTS FILED WITH THE SEC, AS WELL AS ANY AMENDMENTS OR SUPPLEMENTS TO THESE DOCUMENTS, CAREFULLY AND IN THEIR ENTIRETY BECAUSE THEY CONTAIN OR WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Investors and security holders are able to obtain free copies of the registration statement and solicitation statement/prospectus and other documents once they are filed with the SEC by NantKwest through the website maintained by the SEC at www.sec.gov. In addition, investors and security holders are able to obtain free copies of the prospectus and other documents filed with the SEC on NantKwest’s website at www.ir.nantkwest.com.
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The team of doctors and scientists at iosBio believe that the next great leap forward in immunization will be oral delivery
Enabling the fastest and most cost-effective deployment of vaccines the world has ever seen. This is not just a huge leap forward from a humanitarian perspective, oral vaccine technology also represents a significant commercial opportunity.