お知らせ • Jun 27
Nkarta, Inc. Initiates Clinical Trial of NKX019 in Lupus Nephritis with First Patient in Screening and Announces Pipeline Expansion to Additional Autoimmune Indications
Nkarta, Inc. announced the initiation of Ntrust-1, a multi-center clinical trial of NKX019 in lupus nephritis, with the first patient in screening. The company also announced the clearance by the U.S. Food and Drug Administration (FDA) of its second Investigational New Drug (IND) application for NKX019 in autoimmune disease. With this new IND, Nkarta plans to initiate Ntrust-2, an open-label, multi-center clinical trial of NKX019 for the treatment of systemic sclerosis (SSc, scleroderma), idiopathic inflammatory myopathy (IIM, myositis) and ANCA-associated vasculitis (AAV). NKX019 is an allogeneic, off-the-shelf, chimeric antigen receptor (CAR) NK-cell therapy candidate engineered to deplete CD19-positive cells in B-cell mediated disease. The approach leverages the potential advantages of NK cell therapy, including fludarabine-free lymphodepletion to reduce toxicity, deep and rapid B-cell depletion, and the added utility of on-demand dosing, including repeated dosing as needed. NKX019 is engineered to exert its biologic activity without the need for antibodies or exogenous cytokines. Ntrust-1 and Ntrust-2 are multi-center, open label, dose escalation clinical trials that build on academic studies of durable, drug-free remissions in patients with autoimmune disease after CD19-targeted cell therapy. Both trials will assess the safety of NKX019 in people living with autoimmune diseases as well as its ability to enable long-term remissions via a “reset” of the immune system through the elimination of pathogenic B cells. All patients across both studies will receive three-dose cycles of NKX019 at 1 billion or 1.5 billion cells per dose following single-agent lymphodepletion with cyclophosphamide, an agent with an established safety profile across autoimmune diseases. In the Ntrust-1 study, patients with refractory lupus nephritis receive NKX019 on Days 0, 7 and 14. Patients in Ntrust-1 may also receive additional cycles to restore response. Once initiated, Ntrust-2 will enroll patients with SSc, IIM or AAV into parallel cohorts, and NKX019 will be dosed on Days 0, 3, and 7, a regimen that may be advantageous across all Nkarta clinical trials. Each trial is designed to initially enroll up to 12 patients. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal B-cell function and autoantibody production which results in a range of clinical manifestations, including organ damage and an increased risk of death. Lupus nephritis (LN) is among the most severe manifestations of SLE. Approximately 40% of the estimated 200,000 patients in the U.S. diagnosed with SLE will develop LN. Up to 30% of patients with LN progress to end stage kidney disease, which can be fatal without dialysis or a kidney transplant. Systemic sclerosis (SSc, scleroderma) is a progressive autoimmune disease characterized by inflammation and hardening in the skin and other areas of the body including blood vessels and vital organs, especially the lungs. Aberrant immune responses involving autoantibodies induce an inflammatory response in normal tissues that causes the body to produce excess collagen, leading to tight, hard tissue and injury to blood vessels. There are approximately 100,000 people in the U.S. living with SSc. There are no available treatments to halt or reverse the disease process. Approved therapies focus primarily on disease symptoms and can involve significant side effects. Idiopathic inflammatory myopathy (IIM, myositis) is a group of autoimmune disorders characterized by inflammation, weakness, muscle damage, pain, and compromised quality of life. The disease can affect vital organs and be life-threatening. Across the three major subtypes thought to be driven by B cells, dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and anti-synthetase syndrome (ASyS), there are an estimated 50,000 people in the U.S. living with the disease. Despite approved therapies, many people with myositis have refractory disease. Anti-neutrophilic cytoplasmic autoantibody (ANCA) vasculitis is an autoimmune disease characterized by severe, systemic damage to small blood vessels. ANCAs attach to neutrophils, a type of white blood cell, and cause the neutrophils to attack small blood vessels walls, causing inflammation. Inflamed vessels may rupture or become blocked, leading to clinical symptoms and a systemic inflammatory response. Patients may have disease-related complications, such as life-threatening damage to the kidneys, lungs and other organs, as well as toxicities associated with treatment, such as long-term use of immunosuppressants like glucocorticoids. It is estimated that approximately 140,000 people in the U.S. are living with vasculitis. NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed chimeric antigen receptor (CAR) for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies.