Nkarta Announces IND Clearance of Investigator-Sponsored Trial in Myasthenia Gravis and Opening of Enrollment for Ntrust-2
Nkarta (NKTX) announced the opening of enrollment for Ntrust-2 and IND clearance for an investigator-sponsored trial (IST) evaluating NKX019, their allogeneic CD19-directed CAR NK-cell therapy. Ntrust-2 will evaluate the treatment across three parallel cohorts: systemic sclerosis, myositis, and ANCA-associated vasculitis. The IST will study NKX019 in myasthenia gravis patients.
The treatment protocol involves administering NKX019 on Days 0, 3, and 7 following lymphodepletion with cyclophosphamide. The therapy aims to provide a safe, accessible treatment option for autoimmune diseases through B-cell depletion, potentially enabling long-term remissions via immune system reset.
Patient dosing has begun in both Ntrust-1 and the IST for systemic lupus erythematosus, with preliminary data from Ntrust-1 and Ntrust-2 expected in 2025.
Nkarta (NKTX) ha annunciato l'apertura delle iscrizioni per Ntrust-2 e l'approvazione IND per uno studio sponsorizzato dall'investigatore (IST) che valuta NKX019, la loro terapia CAR NK-cell allogenica diretta contro il CD19. Ntrust-2 valuterà il trattamento in tre coorti parallele: sclerosi sistemica, miopatia e vasculite associata ad ANCA. L'IST studierà NKX019 nei pazienti con miastenia grave.
Il protocollo di trattamento prevede l'amministrazione di NKX019 nei Giorni 0, 3 e 7 dopo linfodeplezione con ciclofosfamide. La terapia mira a fornire un'opzione di trattamento sicura e accessibile per le malattie autoimmuni attraverso la deplezione delle cellule B, potenzialmente consentendo remissioni a lungo termine tramite il ripristino del sistema immunitario.
È iniziata la somministrazione ai pazienti sia per Ntrust-1 che per l'IST per il lupus eritematoso sistemico, con dati preliminari da Ntrust-1 e Ntrust-2 attesi nel 2025.
Nkarta (NKTX) anunció la apertura de inscripciones para Ntrust-2 y la aprobación IND para un ensayo patrocinado por investigadores (IST) que evalúa NKX019, su terapia CAR NK-cell alogénica dirigida al CD19. Ntrust-2 evaluará el tratamiento en tres cohortes paralelas: esclerosis sistémica, miositis y vasculitis asociada a ANCA. El IST estudiará NKX019 en pacientes con miastenia gravis.
El protocolo de tratamiento implica administrar NKX019 en los Días 0, 3 y 7 tras una linfodepleción con ciclofosfamida. La terapia tiene como objetivo proporcionar una opción de tratamiento segura y accesible para enfermedades autoinmunitarias mediante la depleción de células B, lo que podría permitir remisiones a largo plazo a través del restablecimiento del sistema inmunológico.
Ya ha comenzado la dosificación en pacientes tanto en Ntrust-1 como en el IST para lupus eritematoso sistémico, con datos preliminares de Ntrust-1 y Ntrust-2 esperados para 2025.
Nkarta (NKTX)는 NKX019, 그들의 동종 CD19 타겟 CAR NK세포 요법에 대한 연구자인 주관 임상 시험(IST)의 IND 승인을 발표하고 Ntrust-2에 대한 등록을 시작했습니다. Ntrust-2는 세 개의 평행 집단인 전신 경화증, 근염, 그리고 ANCA 관련 혈관염에 대해 치료를 평가할 것입니다. IST는 중증 근무력증 환자를 대상으로 NKX019를 연구할 것입니다.
치료 프로토콜은 사이클로포스파미드를 이용한 림프감소 후 0, 3, 7일에 NKX019를 투여하는 것을 포함합니다. 이 요법은 B세포 제거를 통해 자가 면역 질환에 대해 안전하고 접근 가능한 치료 옵션을 제공하고 면역 체계의 리셋을 통해 장기적인 관해를 가능하게 하는 것을 목표로 합니다.
전신 홍반 루푸스에 대한 Ntrust-1과 IST 모두에서 환자에게 약물 투여가 시작되었으며, Ntrust-1과 Ntrust-2의 초기 데이터는 2025년에 예상됩니다.
Nkarta (NKTX) a annoncé l'ouverture des inscriptions pour Ntrust-2 et l'approbation IND pour un essai sponsorisé par un investigateur (IST) évaluant NKX019, leur thérapie CAR NK-cell allogénique dirigée contre le CD19. Ntrust-2 évaluera le traitement à travers trois cohortes parallèles : sclérose systémique, myosite et vascularite associée à ANCA. L'IST étudiera NKX019 chez les patients atteints de myasthénie gravis.
Le protocole de traitement implique l'administration de NKX019 aux Jours 0, 3 et 7, après une lymphodéplétion par cyclophosphamide. La thérapie vise à fournir une option de traitement sûre et accessible pour les maladies auto-immunes grâce à la déplétion des cellules B, permettant potentiellement des rémissions à long terme par un réinitialisation du système immunitaire.
La posologie pour les patients a commencé à la fois dans Ntrust-1 et l'IST pour le lupus érythémateux systémique, avec des données préliminaires de Ntrust-1 et Ntrust-2 attendues en 2025.
Nkarta (NKTX) hat die Eröffnung der Einschreibung für Ntrust-2 und die IND-Zulassung für eine vom Prüfer gesponserte Studie (IST) bekannt gegeben, die NKX019, ihre allogene CD19-geführte CAR NK-Zelltherapie, evaluiert. Ntrust-2 wird die Behandlung in drei parallelen Gruppen untersuchen: systemische Sklerose, Myositis und ANCA-assoziierte Vaskulitis. Die IST wird NKX019 bei Patienten mit Myasthenia gravis untersuchen.
Das Behandlungsprotokoll sieht vor, NKX019 an den Tagen 0, 3 und 7 nach einer Lymphodepletion mit Cyclophosphamid zu verabreichen. Die Therapie zielt darauf ab, eine sichere, zugängliche Behandlungsoption für Autoimmunerkrankungen durch eine Depletion von B-Zellen zu bieten und möglicherweise langfristige Remissionen durch einen Reset des Immunsystems zu ermöglichen.
Die Patientendosierung hat sowohl in Ntrust-1 als auch im IST für systemischen Lupus erythematodes begonnen, wobei erste Daten von Ntrust-1 und Ntrust-2 für 2025 erwartet werden.
- Expansion into four new autoimmune disease indications, broadening market potential
- Treatment protocol allows for on-demand and repeated dosing as needed
- Therapy designed to enable long-term remissions without chronic dosing
- Clinical data not expected until 2025
- Early-stage trials with uncertain outcomes
Insights
The expansion of NKX019 trials into multiple autoimmune indications represents a significant development in the CAR NK-cell therapy space. The program now targets five major autoimmune conditions: systemic sclerosis, myositis, ANCA-associated vasculitis, myasthenia gravis and lupus. This broad approach significantly expands the potential market opportunity.
The therapy's key advantages include rapid B-cell depletion without expansion requirements, reduced toxicity through fludarabine-free lymphodepletion and flexible dosing options. The cyclophosphamide-based lymphodepletion protocol is particularly noteworthy as it has an established safety profile in autoimmune conditions.
The potential for achieving long-term remissions through immune system "reset" could be transformative for these chronic conditions, particularly in myasthenia gravis where current treatments require lifelong immunosuppression. Clinical data expected in 2025 will be important for validating this approach.
This pipeline expansion significantly strengthens Nkarta's market position in the growing cell therapy sector. The addressable market is substantial, as these autoimmune conditions collectively affect millions of patients globally. The company's strategic focus on multiple indications reduces clinical development risk through diversification.
The therapy's potential to achieve drug-free remissions could be particularly disruptive to the current treatment paradigm, which relies heavily on chronic medication. This could translate into significant market opportunity if clinical trials demonstrate durable responses. The involvement of prestigious research institutions (UC Irvine, University of Kansas, Columbia) adds credibility to the development program.
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, Calif., Dec. 05, 2024 (GLOBE NEWSWIRE) -- 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.
Cautionary Note on Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," “plans,” “potential,” "projects,” “would” and "future" or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include, but are not limited to, statements concerning Nkarta’s expectations regarding any or all of the following: Nkarta’s position, plans, strategies, and timelines for the continued and future clinical development and commercial potential of NKX019 (including the plans for the investigator-sponsored clinical trial in myasthenia gravis and the future availability and disclosure of clinical data and other updates from Nkarta’s clinical trials); and the therapeutic potential, accessibility, tolerability, advantages, and safety profile of NK cell therapies, including NKX019 for the treatment of autoimmune diseases, such as lupus, systemic sclerosis, myositis, vasculitis, and myasthenia gravis.
Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Nkarta’s limited operating history and historical losses; Nkarta’s lack of any products approved for sale and its ability to achieve profitability; the risk that the results of preclinical studies and early-stage clinical trials may not be predictive of future results; Nkarta’s ability to raise additional funding to complete the development and any commercialization of its product candidates; Nkarta’s dependence on the clinical success of NKX019; that Nkarta may be delayed in initiating, enrolling or completing its clinical trials; competition from third parties that are developing products for similar uses; Nkarta’s ability to obtain, maintain and protect its intellectual property; Nkarta’s dependence on third parties in connection with manufacturing, clinical trials and pre-clinical studies; and the complexity of the manufacturing process for CAR NK cell therapies.
These and other risks and uncertainties are described more fully in Nkarta’s filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of Nkarta’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, filed with the SEC on November 7, 2024, and Nkarta’s other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Nkarta undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Nkarta Media/Investor Contact:
Greg Mann
Nkarta, Inc.
gmann@nkartatx.com
FAQ
What autoimmune conditions will Nkarta's (NKTX) Ntrust-2 trial evaluate?
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