Lupus Therapeutics to support development of NK cell therapy

FDA recently cleared clinical trial to test NKX019 in lupus nephritis patients

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by Lindsey Shapiro |

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Lupus Therapeutics will partner with Nkarta to advance the development of NKX019, Nkarta’s investigational natural killer (NK) cell therapy, for people with treatment-resistant lupus nephritis, a serious complication of lupus that features kidney damage and dysfunction.

The U.S. Food and Drug Administration (FDA) recently cleared the launch of a clinical trial to test NKX019 in this patient group. The approach is already being tested for non-Hodgkin lymphoma, a type of cancer, but this will be the first to evaluate it in lupus nephritis.

So far, Lupus Therapeutics, the clinical research affiliate of the Lupus Research Alliance (LRA), has provided Nkarta with advisory services. It will also support the early development of NKX019 at select sites of its Lupus Clinical Investigators Network (LuCIN), which consists of top academic centers in North America.

“Lupus Therapeutics is pleased to collaborate with innovative biopharmaceutical companies such as Nkarta to accelerate the clinical evaluation of cell therapies as they advance through development,” Stacie Bell, PhD, Lupus Therapeutics’ executive vice president, said in a press release. “Our advisory services focus on engaging the experts in the scientific community, as well as those living with lupus, as key contributors to treatment development endeavors to increase the probability of success.”

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The promise of cell-based therapy

In lupus, self-reactive antibodies produced by immune B-cells mistakenly attack tissues in the body. Lupus nephritis is a serious complication that affects the kidneys. Limited treatment options are available for it.

Cell-based approaches to help other components of the immune system destroy these self-reactive B-cells are of therapeutic interest for treating the disease.

“Cell therapies, a potential curative therapy like none other for lupus to date, are generating significant interest among top researchers within our Lupus Clinical Investigators Network and the lupus community,” Bell said.

First-generation approaches have focused on immune T-cells, with some early research supported by LRA funding.

This involves collecting a person’s immune T-cells and engineering them to equip them with a lab-made protein — a chimeric antigen receptor, or CAR — that specifically binds to proteins on B-cells. When the modified T-cells are returned to the body, they should target and kill B-cells.

Before being returned, however, a patient must undergo a round of chemotherapy (lymphodepletion) to clear self-reactive immune cells and make room for the modified ones.

How is NKX019 different?

NKX019 modifies NK cells, the body’s first line of defense against viruses and cancer. These cells are engineered to be equipped with a CAR that recognizes the CD19 B-cell protein and contain a version of an immune signaling protein called interleukin-15 on their surface that helps sustain their therapeutic activity.

The company believes the NK strategy may be safer than conventional CAR T-cell therapies, which often trigger serious immune reactions. NK cells don’t release the same inflammatory molecules that drive the side effects associated with T-cells. This type of cell therapy may also reduce the need for lymphodepletion, which comes with a range of side effects.

Rather than using a patient’s own cells like the so-called autologous cell therapies, NKX019 uses healthy donor cells that can be given to many different patients, called an allogeneic approach. The therapy also can be be made in large batches and offered off the shelf, or ready to use, rather than requiring it to be built on demand for each patient. This makes treatment less burdensome.

The planned open-label, dose-escalation trial will assess the safety, effectiveness, and clinical activity of NKX019 in up to 12 patients with treatment-resistant, or refractory, lupus nephritis. After a round of chemotherapy, the participants will receive a three-dose cycle of NKX019 at one of two doses. The first patient is expected to be enrolled in the first half of next year.