Anti-CD 19 CAR-T Cell Therapy in Patients with ANCA Vasculitis: a Two-stage Interventional, Prospective, Open-label, Phase I/II Trial in Patients with Active, Treatment Refractory, ANCA-IgG-positive Vasculitis

The goal of this phase I/II clinical trial is to investigate anti-CD 19 chimeric antigen receptor T cell (CAR-T cell) therapy in patients with antineutrophil cytoplasmic antibodies (ANCA) immunoglobulin (IgG) positive ANCA associated vasculitis (AAV).
The main questions it aims to answer are:
* To assess the safety of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory, ANCA-IgG-positive AAV
* To assess the clinical efficacy of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory ANCA-IgG-positive AAV
* To assess the ANCA seroconversion rate in subjects with active, treatment refractory ANCA-IgG-positive AAV
Participants will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR-T cell immunotherapy. Follow-up time is 52 weeks with regular visits at the site.

开始日期2025-01-01

申办/合作机构

Kyverna Therapeutics, Inc.初创企业

NCT06475495

/ Not yet recruiting临床1/2期IIT

Comparison of B-cell Depletion by Rituximab and Anti-CD 19 CAR-T Therapy in Patients With Rheumatoid Arthritis. Two-stage Interventional, Prospective, Randomized, Controlled, Open Label, Parallel-group Phase I/II Trial in Patients With Active, ACPA-positive and Treatment Refractory Rheumatoid Arthritis

The goal of this phase I/II clinical trial is to compare B-cell depletion by rituximab and anti-CD 19 CAR-T therapy in patients with rheumatoid arthritis. The main questions it aims to answer are:
* To assess the safety of anti-CD19 CAR T cell therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-I)
* To assess the safety of anti-CD19 CAR T cell therapy and of rituximab in subjects with active, ACPA positive and treatment refractory RA (Phase-II)
* To assess ACPA seroconversion after anti-CD19 CAR T cell or rituximab therapy in subjects with active, ACPA positive and treatment refractory RA (Phase-II)
Participants in the test-arm will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR T-cell immunotherapy. In the comparator group patients will receive 2x1 g Rituximab i.v.
Follow-up time (both arms) is 52 weeks with regular visits at the site.

开始日期2024-11-01

申办/合作机构

Kyverna Therapeutics, Inc.初创企业

NCT06588491

/ Recruiting临床2期

KYSA-8: A Phase 2 Open-Label, Single-Arm, Multicenter Study of KYV 101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T Cell (CD19 CAR T) Therapy, in Subjects With Treatment Refractory Stiff Person Syndrome

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Treatment Refractory Stiff Person Syndrome

开始日期2024-09-25

申办/合作机构

Kyverna Therapeutics, Inc.初创企业

100 项与 KYV-101 相关的临床结果

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100 项与 KYV-101 相关的转化医学

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100 项与 KYV-101 相关的专利（医药）

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项与 KYV-101 相关的文献（医药）

2025-02-01·CYTOTHERAPY

Successful generation of fully human, second generation, anti-CD19 CAR T cells for clinical use in patients with diverse autoimmune disorders

Article

作者: Distler, Jörg H W ; Mackensen, Andreas ; Mougiakakos, Dimitrios ; Haghikia, Aiden ; Schroers, Roland ; Krönke, Gerhard ; Schett, Georg ; Gutman, Jonathan ; Dietrich, Sascha ; Sengupta, Ranjita ; Gold, Ralf ; Bayer, Ruthee ; Walker, Karen ; Kröger, Nicolaus ; Heesen, Christoph ; Distler, Jörg H.W. ; Lorente, Mario ; Furie, Richard ; Register, Ames ; Podoll, Amber ; Bullinger, Lars ; Pendleton, Michael

BACKGROUND:

B-cell targeting chimeric antigen receptor (CAR) T-cell therapies, which lead to profound B-cell depletion, have been well-established in hematology-oncology. This deep B-cell depletion mechanism has prompted the exploration of their use in B-cell driven autoimmune diseases. We herein report on the manufacturing of KYV-101, a fully human anti-CD19 CAR T-cell therapy, derived from patients who were treated across a spectrum of autoimmune diseases.

METHODS:

KYV-101 was manufactured from peripheral blood-derived mononuclear cells of 20 patients across seven autoimmune disease types (neurological autoimmune diseases, n = 13; rheumatological autoimmune diseases, n = 7). Patients ranged from 18 to 75 years of age. Duration of disease ranged from <1 to 23 years since diagnosis. Patients were heavily pretreated, and most were refractory to prior immunosuppressive treatments. Apheresis was collected across nine sites, cryopreserved, and shipped to the manufacturing facility. Healthy donor apheresis samples were collected for manufacturing comparison. Manufacturing was performed using the CliniMACS Prodigy system. Cells were enriched for CD4⁺/CD8⁺ T cells, transduced with a third generation lentiviral vector encoding the CAR, expanded in vitro, and harvested. Percent cell viability, T-cell purity, cellular expansion, and transduction efficiency were assessed. Activity was assessed using cytokine release assays for KYV-101 CAR T cells co-cultured with different CD19^+/- target cell lines.

RESULTS:

KYV-101 was successfully manufactured for 100% of patients. Transduced cell populations were highly viable, with expansion ranging from 11 to 66 fold at Day 8, and were comparable across disease types. Healthy donor-derived controls displayed similar expansion ranges. High CAR expression and transduction rates were observed, ranging between 37 and 77% with low variation in transgene copy number (two to four per cell). Cell viability of the final KYV-101 drug product ranged from 87 to 97%. KYV-101 displayed robust CD19-dependent and effector dose-related release of the pro-inflammatory cytokine IFN-γ.

CONCLUSIONS:

KYV-101 manufacturing yielded a CAR T-cell product with high viability and consistent composition and functionality, regardless of disease indication, pre-treatment, and heterogeneity of the incoming material. Cryopreservation of the apheresis and final drug product enabled widespread distribution. These results support the robustness of the manufacturing process for the fully human KYV-101 anti-CD19 CAR T-cell therapy drug product for patients across diverse autoimmune disease types.

2024-06-25·PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Successful use of anti-CD19 CAR T cells in severe treatment-refractory stiff-person syndrome

Article

作者: Borie, Dominic ; Gold, Ralf ; Schroers, Roland ; Geis, Christian ; Haghikia, Aiden ; Sgodzai, Melissa ; Mougiakakos, Dimitrios ; Faissner, Simon ; Motte, Jeremias

Treatment with autologous chimeric antigen receptor (CAR) T cells has emerged as a highly effective approach in neuroimmunological disorders such as myasthenia gravis. We report a case of successful anti-CD19 CAR T cell use in treatment-refractory stiff-person syndrome (SPS). To investigate clinical and immunological effects of anti-CD19 CAR T cell use in treatment-refractory SPS, a 69-y-old female with a 9-y history of treatment-refractory SPS with deteriorating episodes of stiffness received an infusion of autologous anti-CD19 CAR T cells (KYV-101) and was monitored clinically and immunologically for more than 6 mo. CAR T cell infusion resulted in reduced leg stiffness, drastic improvement in gait, walking speed increase over 100%, and daily walking distance improvement from less than 50 m to over 6 km within 3 mo. GABAergic medication (benzodiazepines) was reduced by 40%. KYV-101 CAR T cells were well tolerated with only low-grade cytokine release syndrome. This report of successful use of anti-CD19 CAR T cells in treatment-refractory SPS supports continued exploration of this approach in SPS and other B cell–related autoimmune disorders.

2024-06-01·Transplantation and cellular therapy

Fully Human Anti-CD19 CAR T Cells Derived from Systemic Lupus Erythematosus Patients Exhibit Cytotoxicity with Reduced Inflammatory Cytokine Production

Article

作者: Aigner, Michael ; Park, Soo ; Taubmann, Jule ; Lutzny-Geier, Gloria ; Mackensen, Andreas ; Dingfelder, Janin ; Schett, Georg ; Minopoulou, Ioanna ; Cheng, Joseph K ; Kaplan, Charles D ; Van Blarcom, Tom

KYV-101 is an autologous anti-CD19 chimeric antigen receptor (CAR)-T cell therapy under investigation for patients with B-cell driven autoimmune diseases. Hu19-CD828Z is a fully human anti-CD19 CAR designed and demonstrated to have a favorable clinical safety profile. Since anti-CD19 CAR T cells target and kill B cells in both circulation and tissues, the treatment with Hu19-CD828Z CAR T cells offers great potential in depleting autoreactive B cells. Demonstrate that Hu19-CD828Z CAR T cells manufactured from cryopreserved leukaphereses from patients with systemic lupus erythematosus (SLE) exhibit CAR-mediated and CD19-dependent cytokine release, proliferation and cytotoxicity when co-cultured with autologous primary B cells. T cells were enriched from cryopreserved leukaphereses from SLE patients or healthy donors (HD). CAR T cells were generated by transducing these cells with a lentiviral vector encoding Hu19-CD828Z. CAR-mediated and CD19-dependent activity was monitored in vitro in a set of cytotoxicity, cytokine release, and proliferation studies, in response to autologous primary CD19⁺ B cells, a CD19⁺ cell line (NALM-6), or a CD19^- cell line (U937). Hu19-CD828Z CAR T cells produced from SLE patients or HD induced greater proliferation and dose-dependent cytotoxicity against both autologous primary B cells and the CD19⁺ NALM-6 cells than nontransduced control T cells or co-cultures with a CD19^- cell line. Interestingly, there was lower inflammatory cytokine production from SLE patient-derived CAR T cells compared to HD donor-derived CAR T cells with either CD19⁺ cells or primary B cells. Hu19-CD828Z CAR T cells generated from SLE patient lymphocytes demonstrate CAR-mediated and CD19-dependent activity against autologous primary B cells with reduced inflammatory cytokine production supporting KYV-101 as a novel potential therapy for the depletion of pathogenic B cells in SLE patients.

132

项与 KYV-101 相关的新闻（医药）

2025-01-13

·PRNewswire

Kyverna Therapeutics to Highlight Near-Term Strategic Priorities and Key Milestones at the 43rd Annual J.P. Morgan Healthcare Conference

Extending Company's leadership position in autoimmune CAR T with prioritized indication strategy; pivoting to late-stage development and commercialization First-to-market opportunity with KYV-101 in stiff person syndrome; 40% enrolled in pivotal Phase 2 trial with first BLA filing targeted for 2026; fast-follow indications in myasthenia gravis and lupus nephritis Efficiently expanding into broader autoimmune indications and increasing patient reach with KYV-102 using whole blood rapid manufacturing Cash runway into 2027 to deliver key milestones EMERYVILLE, Calif., Jan. 13, 2025 /PRNewswire/ -- Kyverna Therapeutics, Inc. (Kyverna, NASDAQ: KYTX), a clinical-stage biopharmaceutical company focused on developing cell therapies for patients with autoimmune diseases, announced it will present its 2025 strategic priorities and key milestones during a presentation that will be made by Chief Executive Officer, Warner Biddle, at the 43rd Annual J.P. Morgan Healthcare Conference today, Monday, January 13, 2025. "2025 will be a transformational year for Kyverna as we accelerate our next wave of growth and pivot to late-stage development and commercialization with our differentiated CD19 CAR T construct, KYV-101," said Warner Biddle, Chief Executive Officer, Kyverna. "Building upon our leadership position, we have sharpened our focus and execution on a prioritized set of opportunities – stiff person syndrome, myasthenia gravis and lupus nephritis – each with a clear and rapid path to market, where we can deliver a profound patient impact. Importantly, these indications serve as a beachhead to other neuroinflammatory and rheumatologic diseases, which we will continue to pursue in a capital-efficient manner alongside next-generation innovations, starting with KYV-102, designed to broaden access to CAR T." Mr. Biddle added, "We are pleased with our clinical progress to date, having 40% of patients enrolled in KYSA-8, our pivotal KYV-101 Phase 2 trial in stiff person syndrome, which enables us to target a BLA filing in 2026 and puts us on track to deliver the first approved CAR T therapy in an autoimmune disease. Our fast-follow indication, myasthenia gravis, has already enrolled patients in a company-sponsored trial, KYSA-6, and we expect to report interim Phase 2 data in the second half of 2025." Strategic priorities for the upcoming year include : Focused execution on company-sponsored KYSA studies evaluating KYV-101 in priority indications that offer a clear and rapid path to market. This includes advancing ongoing clinical studies in stiff person syndrome (KYSA-8), myasthenia gravis (KYSA-6), and lupus nephritis (KYSA-1 and KYSA-3). Continue regulatory interactions leveraging the U.S. Food and Drug Administration's Regenerative Medicine Advanced Therapy and Orphan Drug designations for stiff person syndrome and myasthenia gravis. Evaluate additional opportunities in a capital-efficient manner, harnessing investigator-initiated trials (IITs) and other KYSA studies – including multiple sclerosis, systemic sclerosis, and others – to inform the next priority indications for the Company to advance into late-stage development. Advance next-generation innovations, including KYV-102, incorporating the Company's whole-blood rapid manufacturing approach, which aims to improve the CAR T patient experience, eliminate apheresis and ultimately broaden CAR T access. Anticipated Milestones: Based on these strategic priorities, Kyverna has issued the following guidance on upcoming program milestones: Stiff Person Syndrome: Complete pivotal Phase 2 enrollment mid-2025 Report topline pivotal Phase 2 data 1H 2026 BLA filing in 2026 Myasthenia Gravis: Confirm registrational path with regulators 1H 2025 Report interim Phase 2 data 2H 2025 Lupus Nephritis: Report Phase 1 data 2H 2025 Future pipeline: File KYV-102 investigational new drug application 2H 2025 The Company has a cash runway into 2027 to deliver on these key inflection points, with $321.6 million of cash, cash equivalents, and marketable securities as of September 30, 2024. Presentation at the J.P. Morgan Healthcare Conference Warner Biddle will present a company overview at the 43rd Annual J.P. Morgan Healthcare Conference today, January 13, 2025, at 5:15 PM PT. A live webcast of the presentation will be available on the Investors section of Kyverna's website, . A replay of the webcast will be available on Kyverna's website for approximately 30 days following the conference. About KYV-101 Uniquely designed, KYV-101 is an autologous, fully human CD19 CAR T-cell product candidate with highly potent CD28 co-stimulation and designed for tolerability, which is under investigation for B-cell-driven autoimmune diseases. With KYV-101, Kyverna is pioneering a durable disease-clearing approach aiming for deep B cell depletion, an immune system reset, and long-term remission in autoimmune diseases. It is currently being evaluated in company sponsored, open-label, Phase 2 trials in stiff person syndrome and myasthenia gravis and Phase 1/2 trials for lupus nephritis, as well as in investigator-initiated trials and company-sponsored trials for multiple indications. The clinical experience to date with KYV-101 highlights the potential for transformative clinical outcomes in autoimmune patients. About KYV-102 KYV-102 leverages the same fully human, clinically validated CD19 CAR-T construct as KYV-101. It incorporates the Ingenui-T platform, a proprietary, next-generation process that utilizes whole blood with a rapid manufacturing approach. Kyverna intends to broaden CAR T patient access with KYV-102 by eliminating the need for apheresis starting material and reducing the manufacturing turnaround time from conventionally manufactured CAR T products. About Kyverna Therapeutics Kyverna Therapeutics, Inc. (Nasdaq: KYTX) is a clinical-stage biopharmaceutical company focused on liberating patients through the curative potential of cell therapy. Kyverna's lead CAR T-cell therapy candidate, KYV-101, is advancing through clinical development with Phase 2 trials for stiff person syndrome and myasthenia gravis, and two ongoing multi-center Phase 1/2 trials for patients with lupus nephritis. The Company is also harnessing investigator-initiated trials and other KYSA studies, including in multiple sclerosis and systemic sclerosis, to inform the next priority indications for the Company to advance into late-stage development. Its pipeline includes next-generation CAR T-cell therapies in both autologous and allogeneic formats with properties intended to be well suited for use in B cell-driven autoimmune diseases. For more information, please visit . Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." The words, without limitation, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these or similar identifying words. Forward-looking statements in this press release include, without limitation, those related to: Kyverna's strategic priorities and focus; the status of its Phase 2 trial in stiff person syndrome as a pivotal trial; the potential for KYV-101 to be the first-to-market in stiff person syndrome or the first approved CAR T therapy in autoimmune; the potential for KYV-102 to shorten the manufacturing process and increase patient reach and CAR T access; anticipated milestones and timing thereof, including anticipated timing for the first intended BLA submission for KYV-101 and timing for reporting data as well as expected completion of enrollments; Kyverna's anticipated cash runway; and Kyverna's clinical trials, investigator initiated trials and named-patient activities. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties related to market conditions, the possibility that the FDA or other regulatory agencies may conclude that Kyverna's Phase 2 trial in stiff person syndrome is not sufficient to be registration-enabling and may require additional trials or studies to support its intended BLA submission; and other factors discussed in the "Risk Factors" section of Kyverna's most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q that Kyverna has filed or may subsequently file with the U.S. Securities and Exchange Commission. Any forward-looking statements contained in this press release are based on the current expectations of Kyverna's management team and speak only as of the date hereof, and Kyverna specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Contact: Investors: [email protected] Media: [email protected] SOURCE Kyverna Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期孤儿药细胞疗法免疫疗法

2024-12-13

·PRNewswire

Kyverna Therapeutics Strengthens Leadership Team to Accelerate Next Phase of Growth

Key Leadership Appointments Bring New Skills and Capabilities to Organization EMERYVILLE, Calif., Dec. 13, 2024 /PRNewswire/ -- Kyverna Therapeutics, Inc. (Kyverna), a clinical-stage biopharmaceutical company focused on developing cell therapies for patients with autoimmune diseases, announced the recent appointments of Dan Maziasz as Chief Business Officer, Cara Bauer as Chief Human Resources Officer, and Tracy Rossin as Senior Vice President of Corporate Affairs, Communications and Investor Relations. "I'm pleased to welcome three industry leaders to our Kyverna team," said Warner Biddle, Chief Executive Officer of Kyverna. "Dan, Cara and Tracy bring important new skills and capabilities to Kyverna as we continue to support the company's next phase of growth and work to bring a transformative change to patients living with severe autoimmune diseases." Mr. Maziasz brings over 25 years of leadership and business experience across several leading biotechnology and large pharmaceutical companies. Mr. Maziasz most recently served as Chief Business Officer at Atara Biotherapeutics, the first company in the world to receive regulatory approval of an allogeneic T-cell immunotherapy. At Atara, Mr. Maziasz led various corporate initiatives including strategic planning, licensing transactions with industry partners, and research collaborations with academic groups. Before his time at Atara, Mr. Maziasz was Vice President, Corporate Strategy and Business Development at Kite Pharma, a global cell therapy leader, prior to its acquisition by Gilead Sciences. Mr. Maziasz also spent more than a decade at Amgen, where he held roles of increasing responsibility in the US, Europe, and Asia across business development, corporate strategy, finance, and commercial functions. Ms. Bauer brings more than 25 years of experience in global human resources leadership to Kyverna, having served most recently as Global Head of Human Resources at Kite, a Gilead Company, where she oversaw all HR strategy and operations during a period of hypergrowth and global expansion which strengthened the company's leadership position in cell therapy. Prior to this role, she served as the Global Head of HR for the Entertainment Division at Riot Games where she worked directly with the founders to build an Entertainment Studio separate from the core gaming business. Ms. Bauer has also held various HR leadership roles at companies such as Netflix, Amgen, Gartner and Novo Nordisk. Ms. Rossin brings more than 20 years of strategic communications experience to Kyverna, having most recently served as the Head of Public Affairs at Kite, where she was responsible for leading corporate, product and employee communications in addition to patient advocacy. Prior to this role, she served as Vice President, Global Head of Communications at Innate Pharma, an oncology-focused biotech company, where she led both corporate and financial communications. Ms. Rossin also spent more than 12 years at AstraZeneca/MedImmune, where she held multiple U.S. and global communications roles for key therapeutic areas across AstraZeneca's portfolio before serving as the Head of Corporate Affairs at MedImmune, the global biologics research and development arm of AstraZeneca. Before joining AstraZeneca, she held various positions at global public relations agencies working with corporate and healthcare related clients. Inducement Grant In connection with the appointment of Mr. Maziasz as Kyverna's Chief Business Officer, on December 9, 2024, Kyverna granted Mr. Maziasz an option to purchase 350,000 shares of its common stock (Option). The Option was granted pursuant to the Kyverna Therapeutics, Inc. 2024 Inducement Equity Incentive Plan, as approved by the Compensation Committee of Kyverna's Board of Directors on September 14, 2024, and was granted as an inducement material to Mr. Maziasz's employment with Kyverna in accordance with Nasdaq Listing Rule 5635(c)(4). The exercise price of the Option was $4.86, the closing price of Kyverna's common stock on December 9, 2024, the date of grant. The Option will vest over four years, with 25% of the total number of shares subject to the Option vesting on the one-year anniversary of Mr. Maziasz's appointment and 1/48th of the total number of shares subject to the Option vesting monthly thereafter, subject in each case to Mr. Maziasz's continued service to Kyverna on each vesting date. Kyverna is providing this information in accordance with Nasdaq Listing Rule 5635(c)(4).  About Kyverna Therapeutics Kyverna Therapeutics, Inc. (Nasdaq: KYTX) is a patient-centered, clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases. Our lead CAR T-cell therapy candidate, KYV-101 is advancing through clinical development with sponsored clinical trials across two broad areas of autoimmune disease: rheumatology and neurology, including Phase 2 trials for stiff-person syndrome, multiple sclerosis and myasthenia gravis, a Phase 1/2 trial for systemic sclerosis, and two ongoing multi-center Phase 1/2 trials in the United States and Germany for patients with lupus nephritis. Kyverna's pipeline includes next-generation CAR T-cell therapies in both autologous and allogeneic formats with properties intended to be well suited for use in B cell-driven autoimmune diseases. For more information, please visit . Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements." The words, without limitation, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these or similar identifying words. Forward-looking statements in this press release include, without limitation, those related to: the potential impact of the clinical outcomes from the ongoing clinical programs; the potential impact of the new data on the treatment efficacy and safety profile of KYV-101; the potential that the results of the ongoing trials could drastically change the treatment landscape for the targeted autoimmune diseases; Kyverna's goals to develop certain paradigm-shifting treatment options; the potential for KYV-101 to provide durable, immunosuppressant-free remission for autoimmune disease patients; Kyverna's beliefs about the differentiated properties of KYV-101; and Kyverna's clinical trials, investigator-initiated trials and named-patient activities. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties related to market conditions, and other factors discussed in the "Risk Factors" section of Kyverna's most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q that Kyverna has filed or may subsequently file with the U.S. Securities and Exchange Commission. Any forward-looking statements contained in this press release are based on the current expectations of Kyverna's management team and speak only as of the date hereof, and Kyverna specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.  Contact: Investors: [email protected] Media: [email protected] SOURCE Kyverna Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

高管变更临床2期细胞疗法免疫疗法

2024-12-12

·药精通Bio

自免疾病: 系统性红斑狼疮 (SLE) 的靶向治疗进展

系统性红斑狼疮（SLE，Systemic lupus erythematosus）通常称为狼疮，是一种累及多系统的系统性自身免疫性疾病，具有显著的发病率和死亡率。系统性红斑狼疮患者经常会经历疾病发作和缓解的交替时期。SLE 的表现多种多样，从皮疹和关节炎到贫血和血小板减少，再到浆膜炎、肾炎、癫痫发作和精神病。据估计，大约 90% 的 SLE 患者是女性，大多数病例年龄在 15 至 44 岁之间。SLE 女性怀孕被认为是高风险，与一般人群相比，孕产妇和新生儿的发病率和死亡率较高。近年来，精细免疫表型、全基因组关联研究（GWAS）、单细胞测序、多组学分析和基因编辑的进展显着增强了对SLE发病机制的理解。这些技术突破还推动了针对免疫细胞、共刺激分子、细胞因子和信号转导途径的疗法的开发和临床研究，包括单克隆抗体、小分子药物和嵌合抗原受体（CAR-）T细胞免疫疗法。贝利木单抗（Belimumab）和阿尼鲁单抗（Anifrolumab）等治疗方法的批准为临床医生、研究人员和患者提供了更大的信心和更多的选择来治疗中度至重度系统性红斑狼疮，特别是难治性病例。１.　FDA 已批准 SLE 靶向治疗Belimumab（Benlysta） Belimumab（Benlysta）由 GSK 开发，是第一个 B 淋巴细胞刺激剂（BlyS）的靶向抑制剂。通过与 BlyS 结合，Belimumab 抑制 B 细胞（包括自身反应性 B 细胞）的存活，并减少其分化为负责产生免疫球蛋白的浆细胞，尽管它不直接与 B 细胞结合。贝利木单抗最初于 2011 年 3 月获得 FDA 批准用于治疗 SLE，是首个 SLE 靶向疗法，贝利木单抗于 2020 年 12 月获得扩大批准用于治疗狼疮性肾炎。它通常与羟氯喹（Plaquenil）和吗替麦考酚酯（CellCept）等其他药物联合使用，以增强治疗效果。Anifrolumab（Saphnelo） Saphnelo（anifrolumab）是一种全人源单克隆抗体，可与 I 型 IFN 受体的亚基 1 结合，有效阻断 I 型 IFN 的活性。I 型 IFN，例如 IFN-α、IFN-β 和 IFN-κ，是参与调节 SLE 相关炎症途径的细胞因子。在大多数成年 SLE 患者中观察到 I 型 IFN 信号传导活性增加，并且与疾病严重程度相关。作为“首创新药”I 型 IFN 受体拮抗剂，Saphnelo 代表了 SLE 治疗的重大进步。2021年8月2日，美国FDA批准Saphnelo用于治疗中重度SLE。２.　治疗 SLE 的靶向疗法正在开发中表 1. 治疗系统性红斑狼疮的靶向疗法聚乙二醇化抗体 - Dapirolizumab Dapirolizumab pegol 是一种新型研究中人源化无 Fc聚乙二醇 (PEG) 缀合的抗原结合 (Fab') 片段。它抑制 CD40L 信号传导，已被证明可以减少 B 细胞活化和自身抗体产生，减轻 IFN-I 分泌，并减弱 T 细胞和抗原呈递细胞 (APC) 活化。 2024 年 9 月 24 日，UCB 和 Biogen 联合宣布 III 期 PHOENYCS GO 研究评估 dapirolizumab pegol 治疗 SLE 的效果积极。 PHOENYCS GO 是一项多中心、随机、双盲、安慰剂对照、平行的 III 期试验，旨在评估dapirolizumab联合标准护理 (SOC) 疗法与安慰剂加 SOC 疗法在患有以下疾病的患者中的疗效和安全性，包括中度至重度系统性红斑狼疮，共有 321 名患者参与了该研究。分析显示，dapirolizumab pegol 与 SOC 相结合，达到了其主要终点。BICLA方法评估中，第 48 周时，与安慰剂加 SOC 相比，患者的中度至重度疾病活动度显著改善。BICLA 是一个既定的复合终点，用于通过患者病史、临床检查和实验室测试评估临床疾病活动性。此外，评估疾病活动和耀斑的关键次要终点显示出具有临床意义的改善。 dapirolizumab pegol 的安全性与之前的研究一致，并且与接受免疫调节治疗的 SLE 患者的预期安全结果一致。Litifilimab（利替非利单抗） Litifilimab (BIIB059) 由 Biogen 开发，是一种靶向 BDCA2 的全人源化 IgG1 mAb。通过抑制 BDCA2，它可以减少炎症细胞因子（包括 IFN-I）的产生，在调节 SLE 的病理机制中发挥着至关重要的作用。Litifilimab　是目前最先进的BDCA2靶向疗法，已进入治疗皮肤红斑狼疮（CLE）和SLE的III期临床试验。图 1. Litifilimab 的作用机制在一项涉及 SLE 参与者的 2 期试验中，在 24 周内，与安慰剂相比，litifilimab 与基线相比，肿胀和压痛关节的数量有更大程度的减少。需要更长时间和更大规模的试验来确定Litifilimab治疗 SLE 的安全性和有效性。JAK 抑制剂 - Upadacitinib Upadacitinib 是一种选择性、可逆性 JAK 抑制剂，正在研究用于治疗各种严重的免疫介导的炎症性疾病。在细胞和酶活性测定中，与 JAK2、JAK3 和 TYK2 相比，upadacitinib 对 JAK1 显示出特异的强的抑制作用。该药物已被批准用于治疗成人中度至重度类风湿性关节炎、银屑病关节炎、溃疡性结肠炎和强直性脊柱炎。 2023 年，艾伯维宣布了 upadacitinib 的 2 期临床试验取得积极结果，该试验可作为单一疗法或联合使用（elsubrutinib 60 mg 和 upadacitinib 30 mg），用于治疗继续接受标准狼疮治疗的中度至重度 SLE 成人的疗法。基于这些结果，艾伯维表示将推进upadacitinib进入SLE治疗的3期临床试验。S1P1 调节剂 - Cenerimod Cenerimod 是一种潜在的“FIC”、高选择性 S1P1 受体调节剂。这种每日一次的口服片剂正在开发用于治疗系统性红斑狼疮。2022 年 12 月，Idorsia 启动了 OPUS 项目，该项目由两项多中心、随机、双盲、安慰剂对照 3 期试验组成，旨在评估 cenerimod 与中重度 SLE 成人患者的疗效、安全性和耐受性。Cenerimod 已获得美国 FDA 授予的治疗 SLE 的快速通道资格。在 II 期临床试验中，测试的最高剂量为 4 mg，六个月后，与安慰剂相比，治疗组在主要终点（mSLEDAI-2K 评分）上显示出数值改善。然而，除了 4 mg 剂量（p＝ 0.029）外，其他组中没有观察到显着差异。此外，在第 52 周时，所有试验组的 mSLEDAI-2K 和 SRI-4 评分均未发现显著差异。细胞治疗 - KYV-101 KYV-101 是一种新型全人源抗 CD19 嵌合抗原受体 (CAR) T 细胞疗法，旨在用于 B 细胞驱动的自身免疫性疾病。它专门靶向 CD19，这是一种在 B 细胞表面表达的蛋白质。B 细胞除了与许多类型的恶性肿瘤有关，也与自身免疫性疾病相关。 References: [1] Dapirolizumab Pegol Phase 3 Data Presented at the American College of Rheumatology Shows Significant Reduction in Systemic Lupus Erythematosus Disease Activity .[2] Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus,10.1056/NEJMoa2118025 [3]Phase 2 Study of Upadacitinib (RINVOQ®) Alone or as a Combination Therapy Meets Primary and Key Secondary Endpoints in Patients with Systemic Lupus Erythematosus [4] Encouraging Phase 2 data on cenerimod – Idorsia's S1P1 receptor modulator currently investigated for SLE – presented at ACR 2019 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2024类器官前沿应用与3D细胞培养论坛圆满落幕，点击图片可查看会后报告，咨询OTC2025类器官论坛请联系：王晨 180 1628 8769

免疫疗法细胞疗法临床研究临床结果

100 项与 KYV-101 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
抗中性粒细胞胞质抗体相关性血管炎	临床2期	-	Kyverna Therapeutics, Inc.初创企业	2025-01-01
类风湿关节炎	临床2期	-	Kyverna Therapeutics, Inc.初创企业	2024-11-01
坐骨跖骨发育不良	临床2期	美国	Kyverna Therapeutics, Inc.初创企业	2024-09-25
僵人综合征	临床2期	美国	Kyverna Therapeutics, Inc.初创企业	2024-09-25
原发性进行性多发性硬化	临床2期	美国	Kyverna Therapeutics, Inc.初创企业	2024-09-20
继发进展型多发性硬化	临床2期	美国	Kyverna Therapeutics, Inc.初创企业	2024-09-20
重症肌无力	临床2期	美国	Kyverna Therapeutics, Inc.初创企业	2024-08-28
重症肌无力	临床2期	德国	Kyverna Therapeutics, Inc.初创企业	2024-08-28
弥漫性硬皮病	临床2期	美国	Kyverna Therapeutics, Inc.初创企业	2024-08-06
狼疮性肾炎	临床2期	德国	Kyverna Therapeutics, Inc.初创企业	2022-12-01

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06342960 \| NCT05938725 (KYSA-3, PRNewswire) 人工标引	临床1/2期	狼疮性肾炎	6	KYV-101	範餘構顧鹽鹽糧製繭繭(艱築獵構鏇觸窪蓋壓衊) = No High-Grade CRS or ICANS Observed. 餘觸憲憲鑰繭憲餘壓構 (淵網積壓鏇繭鹹繭衊襯 ) 更多	积极	2024-11-14
Company_Website 人工标引	N/A	多发性硬化症 \| 重症肌无力 \| 神经炎性疾病 ... 更多	41	KYV-101	鑰糧遞範襯壓築衊製鑰(願衊獵鏇獵窪窪憲醖願) = In stiff-person syndrome, two patients treated with KYV-101 have demonstrated improved mobility and/or walking speed and reduced autoantibody titers, including one patient at greater than one year post-infusion. A third patient demonstrated reduced autoantibody titers but does not yet have mobility scores available. In myasthenia gravis, three patients treated with KYV-101 have shown reduced pathogenic anti-AChR antibody titers and sustained disease control, including two patients at more than one year post-infusion and all three at greater than 8 months post-infusion. In multiple sclerosis, five patients treated with KYV-101 who failed prior anti-CD20 medications have shown a significant and unprecedented average reduction in oligoclonal bands in the central nervous system (CNS), a potential surrogate biomarker for reduced disease progression. 鏇鹹壓淵齋範構繭蓋簾 (衊觸積積顧製鬱餘選醖 ) 更多	积极	2024-09-18
PRNewswire 人工标引	N/A	僵人综合征	1	KYV-101	窪膚壓廠餘製憲衊窪窪(觸膚蓋製齋艱鏇顧顧選) = 艱艱選醖遞鏇簾襯餘憲壓糧網壓淵繭鏇網願築 (餘衊廠網簾壓鬱餘遞艱 )	积极	2024-06-17
PRNewswire 人工标引	N/A	重症肌无力	1	KYV-101	遞繭鏇醖鹽鹹構獵鏇蓋(襯願廠繭窪簾製選膚醖) = 簾廠鬱齋壓鏇夢淵遞鹽簾選淵築鬱構遞齋選襯 (憲糧觸衊願艱獵鬱鬱餘 ) 更多	积极	2023-11-15