Nantkwest and Frankfurt University Hospital Announce First in Human Dosing of off-the-Shelf HER2.taNK (Car–natural Killer) Cell Therapy in Glioblastoma

CULVER CITY, CA, USA I February 13, 2018 I 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, today announced that the first patient has been dosed in a first-in-human, Phase I clinical study in glioblastoma of HER2.taNK, a novel, natural killer cell-based immuno-oncology therapy using CAR technology in patients. The study is being led by Dr. Michael Burger, principal investigator, together with co-principal investigators Professor Joachim Steinbach, Head of the Institute for Neuro-oncology at the Goethe University Hospital, and Professor Christian Senft, Department of Neurosurgery at the Goethe University Hospital in Frankfurt/Main, Germany.

Natural killer cells are a critical component of the innate immune system and the first line of defense against cancer and viral infections. HER2.taNK is a natural killer cell based therapeutic that has been engineered to incorporate a novel Chimeric Antigen Receptor (CAR) specific for the human epidermal growth factor receptor 2 (HER2).

HER2 is overexpressed in a large percentage of solid tumors, including breast cancer and glioblastoma, representing a well validated target.

The Phase I clinical study is designed to assess the safety, tolerability and efficacy of intracranial injection of HER2.taNK as a single agent therapy in patients with recurrent HER2-positive glioblastoma.

Glioblastoma is the most common and aggressive primary brain tumor in adults and currently incurable. Present standard of care includes surgical resection followed by radiotherapy and chemotherapy. Despite this aggressive treatment, median survival of glioblastoma patients is still only about 15 months, and recurrence remains almost inevitable.

HER2.taNK

NantKwest’s HER2.taNK is designed to provide precise tumor-cell specificity through the use of a CAR construct that employs a HER2-specific scFv antibody fragment for cancer cell recognition and a human CD28.CD3zeta signaling domain.

In pre-clinical studies, HER2.taNK specifically recognized HER2-expressing cells of different tumor origins and displayed high and selective antitumor activity in in vitro and in vivo models (http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(16)30043-0). In addition, HER2.taNK demonstrated selective cytotoxicity against otherwise NK cell resistant glioblastoma cell lines and primary glioblastoma cultures. Antigen specificity and selective cytotoxicity of HER2.taNK was retained in vivo, resulting in antitumoral activity in orthotopic human glioblastoma xenograft models. In immunocompetent mice carrying HER2-expressing murine glioblastoma tumors, treatment with HER2.taNK induced an endogenous antitumor immune response resulting in tumor rejection and long-lasting resistance against tumor re-challenge at distant sites (https://academic.oup.com/jnci/article/108/5/djv375/2412457).

To better inform patient care, these clinical trials will incorporate a state-of-the-art, biomarker analysis using GPS Cancer™, an integrated, multi-omics, whole genome, transcriptome and proteomics molecular analysis provided by NantHealth, an affiliated company. These comprehensive molecular analysis tools are designed to provide critical information to the clinical study team regarding the molecular alterations associated with the patient’s cancer, further enhancing patient care.

The single center, open label clinical study is estimated to enroll 30 participants with recurrent or refractory HER2-positive glioblastoma. A parallel HER2.taNK clinical study is also being planned for the United States that will further expand the study into other solid tumor types. Additional information regarding the clinical study can be found at http://clinicaltrials.gov, NCT03383978.

About NantKwest Inc.

NantKwest (Nasdaq:NK) is 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 inflammatory diseases. NK cells are the body’s first line of defense due to the innate ability of NK cells to rapidly identify and destroy cells under stress, such as cancer or virally-infected cells.

NantKwest’s unique NK cell-based platform, with the capacity to grow active killer cells as a biological cancer therapy, has been designed to induce cell death against cancer or infected cells by three different modes of action: (1) Direct killing using activated NK cells (aNK) that release toxic granules directly into the cell through cell to cell contact, (2) Antibody-mediated killing using haNKs, which are NK cells engineered to incorporate a high affinity receptor that binds to an administered antibody, enhancing the cancer cell killing effect of that antibody, and (3) Targeted activated killing using taNKs, which are NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells.

The aNK, haNK and taNK platform addresses certain limitations of T cell therapies including the reduction of risk of serious "cytokine storms" reported after T cell therapy. As an “off-the-shelf” therapy, NantKwest's NK cells do not rely on a patient’s own often compromised immune system. In Phase 1 clinical trials in patients with late stage cancer, NantKwest's NK cells have been successfully administered as an outpatient infusion therapy without any reported severe side effects, even at doses of 10 billion cells.

By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs that include a Phase 2 trial for a rare form of melanoma and the planned initiation of a clinical trial of NK cells targeted to breast cancer, 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.

SOURCE: NantKwest

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