NKX-019

Ntrust-2 open to enroll patients with systemic sclerosis, myositis and ANCA-associated vasculitis across three parallel cohorts Investigator-Sponsored Trial (IST) expands the development of NKX019 to neuromuscular autoimmune disease myasthenia gravis Patient dosing initiated and enrollment open in Ntrust-1 and IST of NKX019 in systemic lupus erythematosus Clinical data from Ntrust-1 and Ntrust-2 planned for 2025 SOUTH SAN FRANCISCO, CA, USA I December 05, 2024 I Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies, today announced the opening of Ntrust-2 to enrollment and the IND clearance for an investigator-sponsored trial (IST) that will evaluate NKX019, Nkarta’s allogeneic, CD19-directed chimeric antigen receptor (CAR) NK-cell therapy, in patients with myasthenia gravis (MG). Ntrust-2, a multi-center clinical trial, will evaluate NKX019 across three parallel cohorts, including patients with systemic sclerosis (SSc, scleroderma), idiopathic inflammatory myopathy (IIM, myositis) and ANCA-associated vasculitis (AAV). The IST will be led by researchers at the University of California, Irvine and the University of Kansas Medical Center. 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 rapid B-cell killing without the need for cell expansion, a lower risk of toxicities associated with rapid cell expansion, fludarabine-free lymphodepletion to reduce toxicity, and the added utility of on-demand dosing, including the opportunity for repeated dosing as needed. “The expansion to these four autoimmune indications, in addition to continued execution across our existing clinical trials for lupus nephritis and systemic lupus erythematosus, speaks to the promise of our investigational NK cell therapy, NKX019, to provide a safe and accessible treatment option for people living with autoimmune disease,” said Paul J. Hastings, CEO of Nkarta. Ntrust-2 is a multi-center, open label, dose escalation clinical trial that builds on academic studies of durable, drug-free remissions in patients with autoimmune disease after CD19-targeted cell therapy. The trial will enroll patients with SSc, IIM or AAV into parallel cohorts. Per the trial protocol, patients receive NKX019 on Days 0, 3, and 7 following lymphodepletion with cyclophosphamide, an agent with an established safety profile across autoimmune diseases. The trial will assess the safety of NKX019 as well as its ability to enable long-term remissions via a “reset” of the immune system through the elimination of pathogenic B cells. The dual-center, single-arm, open-label Phase 1 IST will be led by Ali A. Habib, M.D., Clinical Professor of Neurology at the University of California, Irvine (UCI), and other investigators. “While the development of new therapies continues to improve outcomes for people living with myasthenia gravis, there remains considerable need for further improvements in clinical outcomes, as well as therapy administration. Most current therapies require ongoing and potentially life-long treatment. Cell therapy has the potential to move away from chronic dosing and change the treatment paradigm for people with myasthenia gravis,” said Dr. Habib. The IST is designed to enroll patients with myasthenia gravis and will evaluate safety and clinical outcomes. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are also planned. Patients will receive NKX019 on Days 0, 3 and 7 following single-agent lymphodepletion with cyclophosphamide. Myasthenia gravis (MG) is an autoimmune disorder where communication between nerves and muscles is disrupted. The condition occurs when the immune system’s B cells produce antibodies that block or damage the neuromuscular junction, leading to muscle weakness and fatigue. Symptoms fluctuate and vary in severity, and in more life-threatening cases, MG can affect muscles responsible for breathing. There is currently no cure for MG, and treatment typically requires chronic immunosuppressive medicines. Preliminary data from Ntrust-1 and Ntrust-2 are anticipated in 2025. As previously announced, a first patient was dosed in Ntrust-1, a clinical trial of NKX019 for the treatment of lupus nephritis, and in an IST of NKX019 for the treatment of systemic lupus nephritis led by researchers at the Columbia University Irving Medical Center. Both studies remain open to enrollment. About Systemic Sclerosis 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. About Myositis 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. About ANCA-associated Vasculitis 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. About SLE Systemic lupus erythematosus (SLE) is an autoimmune disease that causes the body’s immune system to attack its own tissues. The dysregulated immune system produces antibodies that can affect various organs, including the skin, joints, kidneys, heart, and brain. Symptoms can include fatigue, joint pain, or severe life-threatening organ disease. SLE can cause lupus nephritis (LN), a severe complication that affects the kidneys. About the Ntrust Clinical Trials in Autoimmune Disease 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. Per the trial protocols, patients 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. Leveraging the engineering of NKX019, no patients in either trial will receive supplemental cytokines or antibody-based therapeutics. This approach is designed to evaluate the single-agent activity of NKX019 and facilitate a more rapid path to regulatory approval. In the Ntrust-1 study ( NCT06557265 ), patients with refractory lupus nephritis receive three-dose cycles of NKX019 following lymphodepletion. Patients in Ntrust-1 may also receive additional cycles to restore response. Ntrust-2 will enroll patients with systemic sclerosis (scleroderma), idiopathic inflammatory myopathy (myositis), and ANCA-associated vasculitis (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. About the Investigator-Sponsored Clinical Trial of NKX019 for Generalized Myasthenia Gravis The single-arm, open-label Phase 1 investigator-sponsored clinical trial is designed to enroll patients with generalized myasthenia gravis, and will evaluate safety and clinical outcomes. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are planned. Patients will receive NKX019 following single-agent lymphodepletion with cyclophosphamide. The clinical trial is being co-led by Ali A. Habib, M.D., Clinical Professor of Neurology at the University of California, Irvine, and other investigators. About the Investigator-Sponsored Clinical Trial of NKX019 for Systemic Lupus Erythematosus The single-center, single-arm, open-label Phase 1 investigator-sponsored clinical trial is designed to enroll up to 6 patients with systemic lupus erythematosus, regardless of renal involvement, and will evaluate safety and clinical outcomes in a potentially different population than Ntrust-1. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are also planned. Patients receive NKX019 following single-agent lymphodepletion with cyclophosphamide. The clinical trial ( NCT06518668 ) is being led by Anca D. Askanase, M.D., M.P.H., Director, Lupus Center at Columbia University Irving Medical Center and the Director of Rheumatology Clinical Trials. About NKX019 NKX019 is an allogeneic, off-the-shelf on-demand cell therapy candidate designed to deplete CD19-positive B cells, a therapeutic effect which may enable a “reset” of the immune system with the potential for durable remission without chronic therapy in people living with autoimmune disease. NKX019 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. Nkarta is evaluating NKX019 in multiple autoimmune conditions. About Nkarta Nkarta is a clinical-stage biotechnology company advancing the development of allogeneic, off-the-shelf natural killer (NK) cell therapies. By combining its cell expansion and cryopreservation platform with proprietary cell engineering technologies and CRISPR-based genome engineering capabilities, Nkarta is building a pipeline of future cell therapies engineered for deep therapeutic activity and intended for broad access in the outpatient treatment setting. For more information, please visit the company’s website at www.nkartatx.com . SOURCE: Nkarta

The lupus nephritis market is poised for growth, driven by rising disease prevalence, advancements in therapeutics such as biologics and targeted therapies, and increased investment in R&D. Heightened awareness and robust support from governments and key industry players further create a dynamic environment for innovation and better patient outcomes. LAS VEGAS, Dec. 3, 2024 /PRNewswire/ -- DelveInsight's ' Lupus Nephritis Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline lupus nephritis therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the lupus nephritis pipeline domain. Key Takeaways from the Lupus Nephritis Pipeline Report DelveInsight's lupus nephritis pipeline report depicts a robust space with 30+ active players working to develop 35+ pipeline therapies for lupus nephritis treatment. Key lupus nephritis companies such as AstraZeneca, Hoffmann-La Roche, Novartis, Qilu Pharmaceutical, Vera Therapeutics, Conduit Pharmaceuticals, Amgen, Johnson & Johnson, BeiGene, RemeGen, Argenx, Kyverna Therapeutics, Cabaletta Bio, ImmPACT Bio, Alpine Immune Sciences, AlloSite Therapeutics, iCell Gene Therapeutics, Caribou Biosciences, Adicet Bio, Shenzhen Pregene Biopharma Co., Ltd., Resolve Therapeutics, BioAegis Therapeutics, Lepton Pharmaceuticals, Transcenta Holding, and others are evaluating new lupus nephritis drugs to improve the treatment landscape. Promising lupus nephritis pipeline therapies such as Anifrolumab, Obinutuzumab, Ianalumab, QLG1074, Atacicept, AZD1656, Daxdilimab, Nipocalimab, Zanubrutinib, Telitacicept, Efgartigimod alfa, KYV-101, CABA-201, IMPT-514, Povetacicept, ONT01, BCMA-CD19 cCAR T cells, CB-010, ADI-001, PRG-2311, RSLV-621, Recombinant human plasma gelsolin, LN-008, TST 008, and others are under different phases of lupus nephritis clinical trials. In November 2024, Adicet Bio announced that the first LN patient had been dosed in the Phase I clinical trial evaluating ADI-001 in autoimmune diseases. In November 2024, Kyverna Therapeutics announced that it would present updated clinical data from LN patients treated with KYV-101 in ongoing Kyverna-sponsored KYSA-1 and KYSA-3 Phase I/II studies and named patient treatments. In October 2024, Kezar Life Sciences suspended subject enrolment and patient dosing in the Phase II PALIZADE trial of zetomipzomib for active lupus nephritis. In June 2024, Nkarta announced the initiation of Ntrust-I, 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. In June 2024, Adicet Bio announced that the US Food and Drug Administration (FDA) had granted Fast Track Designation to ADI-001 for the potential treatment of relapsed/refractory class III or class IV lupus nephritis. In April 2024, Caribou Biosciences announced that it had received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for CB-010, an allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout (KO), for the treatment of lupus nephritis (LN) and extrarenal lupus (ERL). The Phase 1, multicenter, open label GALLOP clinical trial of CB-010 in patients with LN and ERL is expected to initiate by year-end 2024. In March 2024, Artiva Therapeutics is looking to dose the first patient in a Phase I/II trial assessing its cell therapy AlloNK in lupus nephritis (LN). Request a sample and discover the recent advances in lupus nephritis treatment drugs @ Lupus Nephritis Pipeline Report The lupus nephritis pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage lupus nephritis drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the lupus nephritis clinical trial landscape. Lupus Nephritis Overview Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE), an autoimmune disease that can affect multiple organ systems. In lupus nephritis, the immune system mistakenly attacks the kidneys, leading to inflammation and damage. The exact cause is not fully understood, but it is believed to involve a combination of genetic, hormonal, and environmental factors, including infections and exposure to certain drugs or UV light. Symptoms of lupus nephritis can vary but often include swelling in the legs and feet, high blood pressure, foamy urine, and in severe cases, hematuria. Patients may also experience fatigue, joint pain, and skin rashes, typical of lupus. Diagnosis usually involves a combination of blood tests, urinalysis, and imaging studies. A kidney biopsy may be necessary to evaluate the extent of kidney damage and guide treatment. Treatment for lupus nephritis aims to reduce inflammation and prevent kidney damage. It often involves corticosteroids and immunosuppressive medications such as mycophenolate mofetil or azathioprine. In severe cases, more aggressive treatments, including cyclophosphamide or biologic therapies like belimumab, may be utilized. Regular monitoring of kidney function and overall health is crucial for managing the disease effectively. Find out more about lupus nephritis treatment drugs @ Drugs for Lupus Nephritis Treatment A snapshot of the Lupus Nephritis Pipeline Drugs mentioned in the report: Learn more about the emerging lupus nephritis pipeline therapies @ Lupus Nephritis Clinical Trials Lupus Nephritis Therapeutics Assessment The lupus nephritis pipeline report proffers an integral view of the lupus nephritis emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Lupus Nephritis Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous, Parenteral, Topical Therapeutics Assessment By Molecule Type: Recombinant fusion proteins, Small molecule, Monoclonal antibody, Peptide, Polymer, Gene therapy Therapeutics Assessment By Mechanism of Action: Interferon alpha-beta receptor antagonists, Cell death inhibitors, Cell death stimulants, Antibody-dependent cell cytotoxicity, B-cell activation factor receptor antagonists, Glucokinase stimulants, Dendritic cell inhibitors, Complement factor D inhibitors, Complement C3 inhibitors, Proteasome inhibitors, Natural killer cell replacements, Immunologic cytotoxicity; T lymphocyte replacements Key Lupus Nephritis Companies: AstraZeneca, Hoffmann-La Roche, Novartis, Qilu Pharmaceutical, Vera Therapeutics, Conduit Pharmaceuticals, Amgen, Johnson & Johnson, BeiGene, RemeGen, Argenx, Kyverna Therapeutics, Cabaletta Bio, ImmPACT Bio, Alpine Immune Sciences, AlloSite Therapeutics, iCell Gene Therapeutics, Caribou Biosciences, Adicet Bio, Shenzhen Pregene Biopharma Co., Ltd., Resolve Therapeutics, BioAegis Therapeutics, Lepton Pharmaceuticals, Transcenta Holding, and others. Key Lupus Nephritis Pipeline Therapies: Anifrolumab, Obinutuzumab, Ianalumab, QLG1074, Atacicept, AZD1656, Daxdilimab, Nipocalimab, Zanubrutinib, Telitacicept, Efgartigimod alfa, KYV-101, CABA-201, IMPT-514, Povetacicept, ONT01, BCMA-CD19 cCAR T cells, CB-010, ADI-001, PRG-2311, RSLV-621, Recombinant human plasma gelsolin, LN-008, TST 008, and others. Dive deep into rich insights for new drugs for lupus nephritis treatment, visit @ Lupus Nephritis Drugs Table of Contents For further information on the lupus nephritis pipeline therapeutics, reach out @ Lupus Nephritis Treatment Drugs Related Reports Lupus Nephritis Epidemiology Lupus Nephritis Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical, and forecasted lupus nephritis epidemiology in the 7MM. Lupus Nephritis Market Lupus Nephritis Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key lupus nephritis companies, including NOVARTIS, MORPHOSYS, ASTRAZENECA, ROCHE, KEZAR LIFE SCIENCES, ALEXION PHARMACEUTICALS, CABALETTA BIO, among others. Systemic Lupus Erythematosus Market Systemic Lupus Erythematosus Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key SLE companies, including Biogen, Novartis, MorphoSys, Idorsia Pharmaceuticals, Viatris, RemeGen, UCB Pharma, Genentech, Bristol Myers Squibb, AbbVie, among others. Systemic Lupus Erythematosus Pipeline Systemic Lupus Erythematosus Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key myasthenia gravis companies, including Yake Biotechnology, UCB, Sorrento Therapeutics, SinoMab Bioscience Ltd, Shanghai Junshi Biosciences, Sareum, Sanofi, Roche, Rheos Medicine, Resolve, Provention Bio, Pfizer, Novartis, Neovacs, Merck, Medsenic, Landos Biopharma, Kezar Life Sciences, Kangpu Biopharmaceuticals, Janssen Research & Development, Janssen, InnoCare, ImmuPharma, I-MAB Biopharma, ILTOO, Idorsia Pharmaceuticals, Horizon Therapeutics, Genovax, Exinda Thearapeutics, Equillium, Eli Lilly and Company, Eisai, Daiichi Sankyo Company, Corestem, Corbus Pharmaceuticals, Citryll BV, Chipscreen Biosciences, Carna Bioscience, Bristol-Myers Squibb, Brickell Biotech, Boston Pharmaceuticals, Biogen, Athos Therapeutics, Asahi Kasei Pharma, Aria Pharmaceuticals, Antengene Therapeutics, Amgen, Alpine Immune Sciences, Akeso Biopharma, AbbVie, among others. 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