NantKwest Launches First-in-class, First-in-human Phase I Clinical Trial With a Targeted PD-L1 t-haNK Cell Therapy in Patients With Solid Tumors

First engineered, GMP-grade, cryopreserved, off-the-shelf, bi-specific NK cell therapy to enter human clinical trials targeting PD-L1 and CD16 in patients with solid tumors

NantKwest establishes a leading portfolio of off-the-shelf NK cells at clinical stage of development with three engineered NK92 cells in trials: CD16 targeted haNK, CD19/CD16 targeted t-haNK and now PD-L1/CD16 targeted t-haNK

CULVER CITY, Calif.–(BUSINESS WIRE)–NantKwest Inc. (Nasdaq:NK), a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and other diseases, today announced that the company’s PD-L1 t-haNK investigational new drug application (IND) has cleared FDA review and the program has now transitioned to a first-in-human clinical trial in patients with locally advanced or metastatic solid cancers.

Programmed death-ligand 1 (PD-L1) is a transmembrane protein that plays a major role in suppressing the immune system in many cancer patients. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 establishes an inhibitory signal that reduces the proliferation of antigen-specific T-cells while also reducing apoptosis in suppressive regulatory T cells (Tregs) that further inhibits immune responses.

NantKwest’s PD-L1 t-haNK cell therapy is a novel, NK cell-based immuno-oncology therapy that includes a PD-L1 based Chimeric Antigen Receptor (CAR) engineered into the company’s proprietary haNK NK cell, which also includes the high affinity variant of the CD16 receptor (V158 FcγRIIIa) to mediate antibody dependent cellular cytotoxicity (ADCC). Together, the use of this targeted, bi-specific, next generation PD-L1 t-haNK therapy has been shown in preclinical studies to significantly enhance cancer cell killing and improve overall response rates.

“In just a few short weeks since announcing the FDA clearance of our first bi-specific, engineered NK cell therapy clinical trial using a CD19 t-haNK targeting patients in lymphoma, we are now pleased to announce that the FDA has authorized the company to go forward with our second bi-specific NK cell therapy clinical trial using a PD-L1 t-haNK targeting patients with solid tumors,” commented Dr. Patrick Soon-Shiong, Chairman and CEO of NantKwest. Dr. Soon-Shiong continued, “We plan to synergistically combine a wide range of immunotherapy molecules with our proprietary, multi-targeted, off-the-shelf NK cell therapy, in this case, a PD-L1 t-haNK to explore the unique therapeutic potential of integrating both the innate and adaptive immune systems to achieve durable complete remissions. Based on the FDA clearance, we look to rapidly transition this program to a Phase I human clinical trial designed to assess the safety, tolerability and efficacy of PD-L1 t-haNK cell therapy in patients with solid tumors. Upon completion of this safety phase, NantKwest intends to combine this PD-L1 t-haNK cell therapy with other immunomodulatory agents including NabFc-N803, a IL15 cytokine super agonist and Adenovirus/ yeast vectors delivering tumor associated and neoantigens, as part of an integrative, combination therapy designed to further enhance the therapeutic effectiveness of this novel NK cell-based therapeutic intervention, which we describe as our NANT Cancer Memory Vaccine.”

PD-L1 t-haNK

NantKwest’s PD-L1 t-haNK cell therapy is designed to provide precise tumor-cell specificity through the use of a CAR construct that utilizes a PD-L1-specific scFv (single chain antibody fragment) engineered into the company’s proprietary haNK NK cell that includes the high affinity variant of the CD16 receptor (V158 FcγRIIIa) to mediate antibody dependent cellular cytotoxicity (ADCC). In preclinical studies, cytotoxicity of these GMP-grade, cryopreserved PD-L1 t-haNK cells were comprehensively evaluated against a panel of cancer cell lines with different levels of PD-L1 expression in vitro and in vivo, with these studies showing increased activity and selective cytotoxicity toward a wide range of PD-L1-expressing tumor cells.

To better inform routine patient care, these clinical trials will incorporate a state-of-the-art, biomarker analysis, including GPS Cancer™, which is an integrated, multi-omics, whole genome, transcriptomic platform, provided by NantHealth, an affiliated company. These comprehensive molecular analysis tools are designed to provide critical information to the clinical study team regarding the unique molecular alterations associated with the patient’s cancer and response rates, potentially enhancing patient management.

Additional information regarding the PD-L1 t-haNK clinical study can be found at www.nantkwest.com or www.clinicaltrials.gov/.

About NantKwest

NantKwest, a member of the NantWorks ecosystem of companies, is an innovative clinical-stage immunotherapy company focused on harnessing the power of the innate immune system by using the natural killer cell to treat cancer and virally induced infectious diseases.

NantKwest is uniquely positioned to implement precision cancer medicine, with the potential to change the current paradigm of cancer care. Natural Killer (NK) cells are a safeguard in the human body designed to recognize and detect cells under stress due to cancer or viral infection. NantKwest’s “off-the-shelf” activated NK cell platform is designed to destroy cancer and virally infected cells from the body. The safety of our NK cells as well as their activity against a broad range of cancers have 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. In addition to being a universal cell-based therapy that does not require individualized patient sourcing or matching, our NK cell products have been largely administered in the outpatient setting as an “off-the-shelf” living drug.

With the capacity to grow active killer cells as a cancer therapy, our NK cells have been designed to induce cell death against cancers and virally infected cells by several mechanisms, including: (i) innate killing, whereby all of our NK platforms recognize the stress proteins typically found on cancer cells, which, upon binding, release toxic granules to immediately kill their targets; (ii) antibody-mediated killing with our haNK^® platform, which are NK cells engineered to express antibody receptors that can bind to therapeutic antibody products, thereby enhancing the cancer cell killing effect of that antibody; and (iii) Chimeric Antigen Receptor directed killing using the taNK^® platform, which includes NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells. All three modes of killing (innate, antibody-mediated, and CAR directed killing) are employed by our t-haNK™ platform, which is an innovative combination of our aNK, haNK^® and taNK^® platforms in a single product.

Our haNK^®, and t-haNK™ platforms have been designed to address certain limitations of CAR T-cell therapy including the capability to infuse cell therapy in an outpatient setting which allows for potential reduction of risk for serious cytokine storms and protracted serious adverse events. In phase I and II clinical trials in patients with late stage cancer, our NK cells have been administered as an investigational outpatient infusion safely with greater than 500 infusions to date at a dose of 2 billion cells per infusion.

By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs, we believe NantKwest is uniquely positioned to be the premier immunotherapy company and transform medicine by delivering living drugs in a bag and bringing novel NK cell-based therapies to routine clinical care.

NK-92, aNK, haNK, taNK, and t-haNK are trademarks of NantKwest, Inc.

Forward-Looking Statements

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. Risks and uncertainties related to this endeavor include, but are not limited to, obtaining FDA approval of NantKwest’s NK cells as well as other therapeutics as part of the NANT Cancer Vaccine platform as a cancer treatment.

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 March 31, 2019. 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.

Contacts

Jen Hodson

562-397-3639

[email protected]