ImmunityBio Announces Positive Phase 2 Results Showing That Anktiva Restores the Activity of Checkpoint Inhibitors in Patients Who Have Relapsed Checkpoint Immunotherapy in Non-Small Cell Lung Cancer

CULVER CITY, Calif.--(BUSINESS WIRE)--ImmunityBio, Inc., a privately held immunotherapy company, today announced the presentation of encouraging data in non-small cell lung cancer (NSCLC) from the company’s ongoing Phase 2b study, QUILT-3.055 (ClinicalTrials.gov: NCT03228667) at the International Association for the Study of Lung Cancer (IASCL)’s 2020 World Conference on Lung Cancer, Singapore, being held virtually January 28 – 31, 2021.

The presentation, titled “QUILT 3.055: a phase 2 multi-cohort study of N803 (IL-15 superagonist) in combination with checkpoint inhibitors in NSCLC,” highlighted safety and efficacy data from NSCLC patients in Cohort 1 of the study (N=78), which is evaluating patients with initial response on single-agent checkpoint inhibitor therapy who subsequently progressed on or after that therapy in multiple tumor types. The study is designed to evaluate combination immunotherapy regimens that include ImmunityBio’s lead cytokine infusion protein, a novel interleukin-15 (IL-15) superagonist complex (Anktiva™, also called N-803) in patients who have previously received treatment with PD-1/PD-L1 immune checkpoint inhibitors. Anktiva has been engineered to exhibit a longer half-life and more potent trans-presentation relative to endogenous IL-15 to promote natural killer (NK) cell and T cell expansion to control cancer.

Key presentation results include:

• Clinical benefit was demonstrated in a majority of the NSCLC patients, as measured by reduction of target lesion size and cessation of progression in the target lesion over time (with follow-up of up to 13 months).
• Clinical benefit was observed in patients with immediate prior progression on checkpoint inhibitors when Anktiva was combined with the checkpoint inhibitor, regardless of PD-L1 status or use of chemotherapy with checkpoint inhibitors
• The combination regimen of Anktiva and checkpoint inhibitors was well tolerated, with low incidence of treatment-related severe adverse events in second- and third-line NSCLC patients who had progressed on checkpoint inhibitor therapy at the time of study enrollment.
• Among 78 participants, nine (12%) exhibited grade 3 or higher treatment-emergent adverse events (AEs). Common low-grade AEs observed included injection site reactions (72%), chills (30%), fatigue (27%), fever (26%) and nausea (12%).
• These results suggest that a combination regimen with Anktiva has the potential to restore and or enhance responsiveness to checkpoint inhibitors, including in patients with low PD-L1 expression, which typically is a robust predictor of checkpoint inhibitor failure.

“These encouraging safety and efficacy data suggest that the addition of Anktiva to checkpoint inhibitors has the potential to restore and/or enhance sensitivity to checkpoint inhibitors. While immunotherapy has been transformative for many NSCLC patients, particularly those with high PD-L1 expression, the majority will not experience durable response to these treatments,” said lead investigator John Wrangle, M.D., Associate Professor, Division of Hematology/Oncology at Hollings Cancer Center at the Medical University of South Carolina. “Strikingly, we see clinical benefit in patients with immediate prior progression on checkpoint inhibitors and low PD-L1 expression, groups which historically are less likely to respond to checkpoint inhibitors, without the need for interval chemotherapy or radiation therapy and their attendant toxicities.”

Tumor resistance to checkpoint therapy occurs when T cells are unable to recognize the tumor cell antigen. NK cells can overcome this resistance as indicated by Allen, et al., “Mechanisms of resistance to T cell-based immunotherapy in head and neck cancer” (DOI: 10.1002/hed.26158), who show that NK cells can improve the efficacy of T-cell activated immunotherapy such as checkpoint inhibitors.

Sandeep Bobby Reddy, M.D., Chief Medical Officer at ImmunityBio, commented, “This Phase 2 study demonstrates that activation of NK cells through administration of Anktiva, reactivates and restores the activity of checkpoint inhibitor therapy even in patients who relapsed on the same checkpoint therapy. Thus, the potential exists that Anktiva could be the combination backbone to all checkpoint therapy by activating both NK and T cells. We believe that our particular approach in using an engineered IL-15 superagonist to coordinate T cell and natural killer cell-mediated responses may elicit tumor response, regardless of the type and extent of prior checkpoint inhibitor therapy, PD-L1 status, and tumor type. The data presented are from the NSCLC cohort of a multi-cohort ongoing trial in 11 checkpoint inhibitor indications. Much excitement has been generated with targets such as TIGIT, OX40, TIM3, LAG3 and many others. We are particularly excited that our approach is independent of a particular biomarker and may have a broader applicable patient population.”

Lung cancer is the second most common cancer in men and women (excluding skin cancer), and non-small cell lung cancer accounts for 80% to 85% of all lung cancers, according to the American Cancer Society. In 2021, more than 235,000 people will be diagnosed with lung cancer and more than 131,000 people will die from the disease.

NantKwest Transaction

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.

About ImmunityBio

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.

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 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.

Forward-Looking Statements

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 been verified by any independent source.

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This communication is not intended to and does not constitute an offer to sell or the solicitation of an offer to buy, sell or solicit any securities or any proxy, vote or approval in any jurisdiction pursuant to or in connection with the proposed transaction or otherwise, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offer of securities shall be deemed to be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act.

Additional Information and Where to Find It

In connection with the proposed transaction, NantKwest intends to file a registration statement on Form S-4 with the SEC, which will include a prospectus and joint proxy / solicitation statement of NantKwest and ImmunityBio (the “solicitation statement/prospectus”). 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, WHEN THEY BECOME AVAILABLE, 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 WILL CONTAIN IMPORTANT INFORMATION ABOUT THE PROPOSED TRANSACTION. Investors and security holders will be able to obtain free copies of the registration statement and solicitation statement/prospectus and other documents filed with the SEC by NantKwest through the website maintained by the SEC at www.sec.gov. In addition, investors and security holders will be able to obtain free copies of the prospectus and other documents filed with the SEC on NantKwest’s website at www.ir.nantkwest.com.

Participants in the Solicitation

NantKwest and certain of its respective directors and executive officers may be deemed to be participants in the solicitation of proxies from stockholders of NantKwest in connection with the proposed transaction under the rules of the SEC. Investors may obtain information regarding the names, affiliations and interests of directors and executive officers of NantKwest in NantKwest’s proxy statement for its 2020 annual meeting of stockholders, which was filed with the SEC on April 24, 2020, as well as its other filings with the SEC. Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, will be included in the registration statement, solicitation statement / prospectus and other relevant materials to be filed with the SEC by NantKwest regarding the proposed transaction (if and when they become available). You may obtain free copies of these documents at the SEC’s website at www.sec.gov. Copies of documents filed with the SEC will also be available free of charge from NantKwest using the sources indicated above.