Memory Cytokine-Enhanced Natural Killer Cells Show Promising Results in Leukemia Patients; Data Support ImmunityBio’s Scaled m-ceNK Clinical Program

On March 2, 2022 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported study results that further demonstrate the potential for use of memory-like cytokine-enriched natural killer (m-ceNK) cells for the treatment of cancer (Press release, ImmunityBio, MAR 2, 2022, View Source [SID1234609366]). ImmunityBio has successfully scaled the process of generating over 20 billion m-ceNK cells from a single extraction of white blood cells from a donor or patient, and reports promising clinical data supporting the ongoing development of memory NK cells for the treatment of both liquid and solid tumors of all types.

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In a Phase 2 study sponsored by Washington University School of Medicine (NCT02782546), white blood cells retrieved from HCT donors to treat acute myeloid leukemia (AML) patients, were stimulated with cytokines (IL-12, -15, and -18) to form memory-like NK cells, and were re-infused to the patients, who also received ImmunityBio’s IL-15 superagonist Anktiva (N-803). The cytokine-stimulated NK cells safely augmented a leading treatment for AML-—HLA-haploidentical hematopoietic cell transplantation. The data showed that the cytokine-stimulated NK cells were persistent, showed increased production of interferon-gamma and functionality, and led to a complete response in 87% of patients after Day 28. The results were recently published in a peer-reviewed article ("Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia") in Science Translational Medicine.

NK cells are innate immune cells that are under investigation as a cell therapy for multiple types of cancer. A challenge of NK cell-based therapies, however, is ensuring that the cells persist and remain functional long-term. This study showed that memory-like NK cells derived from the same donor as the hematopoietic cell transplantation (HCT) persisted for at least two months after transplantation and were highly functional ex vivo. Together, these findings support the use of memory NK cells as a component of HCT for leukemia.

"This important study adds to the growing body of data that shows the cancer-fighting ability of NK cells can be enhanced by stimulating expansion and persistence of these cells," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "The study also showed that stimulated memory NK cells are effective with only a single infusion when given along with Anktiva support. To facilitate this approach, ImmunityBio has successfully scaled cytokine enrichment and expansion of m-ceNK cells, so cancer patients can receive multiple infusions of these potent and persistent m-ceNK cells generated from a single donation of white blood cells."

About Memory Cytokine-Enhanced NK Cells (m-ceNK):
ImmunityBio has successfully enriched and expanded NK cells obtained from peripheral blood of donors using a technique called apheresis to generate NK cells with a memory-like phenotype, which exhibit both high cytotoxicity and increased interferon-gamma production. These m-ceNK cells can be generated from an individual donor for autologous cell therapy, but have also been generated as an allogeneic product from cord blood. In addition to the high potential for enhanced efficacy, m-ceNK cells can be infused easily in an outpatient setting.

ImmunityBio has developed a novel method of m-ceNK cells production that yields multiple clinical-dose forms from a single apheresis (white blood cell collection) using the company’s proprietary NANT 001 Bioreactor (GMP-in-a-Box), thereby alleviating pressures on supply of starting material. An optimized cryopreservation protocol for maximum shelf-life and potency upon recovery was also established, a necessity for any off-the-shelf product. ImmunityBio is leveraging their ability to generate m-ceNK cells with potent cytotoxicity, increased IFN-gamma production, proliferative capacity, activation surface markers and memory response to establish a propriety method for generation, expansion, and cryopreservation of these cells for autologous use.

The QUILT 3.076 Study of Cryopreserved M-ceNK cells
Cryopreserved m-ceNK cells in combination with Anktiva (N-803) will be tested in a 2-part Phase 1 study (NCT04898543) designed to evaluate safety in subjects with locally advanced or metastatic solid tumors; solid tumors comprise approximately 90% of adult cancers and 40% of all cancers in children, according to the American Cancer Society. The study will compare the quantity and characteristics of m-ceNK cells collected and cytokine-enriched from newly diagnosed patients who have not received prior treatment to m-ceNK cells generated from patients who have received at least two prior treatments for their cancer.

The study consists of two cohorts and there will be 10 participants in each cohort. Cohort 1 includes participants with newly-diagnosed, high-risk solid tumors who have not received prior treatment; and cohort 2 includes participants with relapsed/refractory (r/r) solid tumors who have progressive disease after receiving ≥ 2 prior therapies. Participants will be enrolled in the two cohorts simultaneously.

Participants in Cohort 1 will participate in apheresis collection of lymphocytes (part A) and will not receive any investigational therapy in this study.
Participants in Cohort 2 will undergo an apheresis collection of lymphocytes (part A) prior to receiving 4 infusions of M-ceNK on days 1, 8, 15 and 22 along with N-803 on days 1 and 15.