Livmoniplimab

关注并星标CPHI制药在线日前，艾伯维「Livmoniplimab 注射液」在国内获得临床试验默示许可，用于治疗肝细胞癌。       Livmoniplimab(ABBV-151/ARGX-115)一款人源化抗GARP(LRRC32)/TGFβ1单抗，最早由Argenx公司与比利时天主教鲁汶大学Duve研究所合作开发，其利用Argenx特有的SIMPLE Antibody技术平台，通过以GARP为靶点，阻止抑制免疫系统攻击恶性肿瘤细胞的转化生长因子-β（TGF-β）的产生。       2016年4月，艾伯维与Argenx公司就Livmoniplimab达成合作协议，交易总额6.85亿美元。2018年8月，艾伯维获得该药的独家许可。       目前，Livmoniplimab被开发联合PD-1抑制剂Budigalimab治疗肝细胞癌、NSCLC等晚期/进展性实体瘤，其中Livmoniplimab+Budigalimab+化疗治疗NSCLC的临床试验已进入3期阶段。       关于GARP/TGF-β1及其靶点进展       GARP（糖蛋白A主导重复序列）是Lrrc32基因编码的一个分子量为72 kDa的I型跨膜蛋白，由662个氨基酸组成。GARP是潜伏性转化生长因子-β1（LTGF-β1）的对接受体，在调节性T淋巴细胞（Tregs）、活化的B细胞和血小板上大量表达。而且，研究发现许多预后不良的癌症都出现GARP表达增加。       GARP是TGF-β1表达和激活的关键调节因子，其通过与LTGF-β1结合，将LTGF-β1集中在细胞表面并增强其活性。在细胞表面，GARP与LTGF-β1复合物与整合素（αVβ6和αVβ8）结合，释放活性TGF-β1。而TGF-β1是一种多效性细胞因子，在细胞增殖、发育、凋亡、纤维化、血管生成、伤口愈合和癌症等生物学过程中发挥重要作用。       GARP/TGF-β1是Treg细胞具有免疫抑制功能的核心机理之一。研究发现，GARP通过调节固有和适应性免疫系统支持TGF-β1驱动的癌细胞生长和扩散，并有利于肿瘤免疫逃避。活性TGF-β1通过直接抑制CD8+细胞毒性T细胞（CTL）的克隆扩增和细胞毒性，损害适应性抗肿瘤免疫。       GARP/TGF-β1被认为是肿瘤治疗的潜力靶点，目前全球药企针对该靶点已有几款药物进入临床试验阶段，详见下表。整体来看，在研GARP/TGF-β1靶向药相对较少，且大多处于早期临床，此外，BMS、先声药业在该领域也有布局，但相关药物处于临床前阶段。       资料来源：公开资料       具体品种上，第一三共的DS-1055a是一种具有增强 ADCC 活性的人源化抗GARP单抗，其通过消耗活化的GARP阳性Treg 细胞显示增强的抗肿瘤免疫力，目前正在实体瘤患者中开展1期临床试验。       济民可信的JYB1907是其自主研发的一款GARP/TGF-β1靶向重组人源化单抗，通过特异性结合GARP/TGF-β1，阻断GARP介导的TGF-β1的释放，逆转肿瘤微环境中的免疫抑制效应，提高抗肿瘤免疫应答。       临床前研究显示JYB1907具有良好的安全性和有效性：在多种人肿瘤细胞PBMC人源化肿瘤动物模型中，JYB1907表现出不同程度的肿瘤生长抑制作用，其中在ZR-75-1人乳腺癌模型中可观察到超过一半比例的小鼠肿瘤完全消退。此外，JYB1907联合抗PD-L1抗体在A375人黑色素瘤模型中诱导了部分小鼠的肿瘤完全消退，显著优于抗PD-L1抗体单用的抑瘤效果。2023年1月，JYB1907在美国获批临床，2023年6月在国内获批临床。       HLX60是复星医药自主研发的创新型抗GARP单抗，通过与GARP结合，特异性阻断GARP介导的TGF-β1的释放，从而解除TGF-β1形成的免疫抑制，提高抗肿瘤免疫应答。而且，HLX60还可以通过抗体依赖细胞介导的细胞毒作用清除GARP阳性肿瘤细胞和Tregs等免疫抑制性细胞，从而发挥抗肿瘤作用。       临床前研究结果显示：HLX60与斯鲁利单抗(PD-1单抗)联用的抗肿瘤效果明显优于斯鲁利单抗或HLX60的单药治疗效果。2022年8月，该药联合斯鲁利单抗治疗晚期/转移性实体瘤的1期临床试验在澳大利亚获批开展。2022年10月，该药在国内获批临床，用于治疗实体瘤和淋巴瘤。       总结       整体来看，GARP/TGF-β1赛道处于早期研发阶段，但其潜力不可小觑。2020年Nature上发表的标题为《选择性抑制GARP表达的Tregs产生的TGF-β1克服了癌症患者对PD-1/PD-L1阻断的耐药性》的文章表明，抗GARP-TGF-β1单抗可以作为一种免疫疗法，通过选择性阻断Treg产生TGF-β1诱导肿瘤消退。目前，GARP靶向药除被开发作为单药疗法，还有望成为PD-1/PD-L1单药的新搭档。【智药研习社近期会议预告】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

$374 million in fourth quarter and $1.2 billion in full year global net product sales sBLA for VYVGART® Hytrulo for CIDP accepted for priority review by FDA with PDUFA target action date of June 21, 2024 On track to report data from six Phase 2 proof-of-concept trials by end of 2024 Management to host conference call today at 2:30 pm CET (8:30 am ET) February 29, 2024, 7:00 am CET Amsterdam, the Netherlands – argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, today reported financial results for the full year 2023 and provided a fourth quarter business update. “argenx reached thousands of new patients and their families in 2023 by delivering on our commitment to make VYVGART available to the global MG community,” said Tim Van Hauwermeiren, Chief Executive Officer of argenx. “This expansion demonstrates that VYVGART has the potential to address the high unmet need for innovation in patients suffering from MG, and moves us closer to sustainability as we build an integrated immunology company. Clinically, we generated significant data through multiple study readouts, achieving key milestones for both the CIDP and MMN patient communities and importantly advancing our second molecule, empasiprubart. Looking forward to 2024, we will act with a continued sense of purpose to expand our patient reach. We will use the learnings and momentum from our gMG launch to strategically lay the groundwork for a potential CIDP approval, leveraging our current infrastructure and deep relationships in the neurology community to position VYVGART SC for success. CIDP patients have been waiting for innovation, and we are eager to translate the transformative ADHERE data into potential benefit for patients as quickly as possible.” FOURTH QUARTER 2023 AND RECENT BUSINESS UPDATE Reaching More Patients with VYVGART VYVGART® (efgartigimod alfa-fcab) is a first-in-class antibody fragment targeting the neonatal Fc receptor (FcRn), and is now approved in more than 30 countries globally for the treatment of generalized myasthenia gravis (gMG). VYVGART subcutaneous (SC) (efgartigimod alfa and hyaluronidase-qvfc) is approved in the U.S. (as VYVGART Hytrulo), Japan (as VYVDURA®) and Europe, making VYVGART the only gMG treatment available as both an IV and simple SC injection. argenx is planning to reach more patients commercially through its multi-dimensional expansion efforts, including patients earlier in the MG treatment paradigm and new patient populations through global regulatory approvals for MG and the expansion of use to treat additional autoimmune indications. Generated global net product revenues (inclusive of both VYVGART and VYVGART SC) of $374 million in the fourth quarter and $1.2 billion in the full year of 2023Medicines and Healthcare products Regulatory Agency (MHRA) approved VYVGART SC in the United Kingdom for the treatment of adult patients with gMG on February 6, 2024, with self-administrationMinistry of Health, Labour and Welfare (MHLW) approved VYVDURA in Japan for the treatment of adult patients with gMG, inclusive of seronegative patients, on January 18, 2024, with self-administrationDecisions on regulatory approvals of VYVGART for gMG expected in Switzerland, Australia, Saudi Arabia and South Korea by end of 2024Decision on approval of VYVGART SC for gMG in China through Zai Lab expected by end of 2024Decision on approval of VYVGART for primary immune thrombocytopenia (ITP) in Japan expected in first quarter of 2024Supplemental Biologics License Application (sBLA) for VYVGART Hytrulo accepted for priority review by FDA for chronic inflammatory demyelinating polyneuropathy (CIDP); Prescription Drug User Fee Act (PDUFA) target action date of June 21, 2024Regulatory submissions of VYVGART SC for CIDP in Japan, Europe, China and Canada expected in 2024Registrational studies to expand VYVGART label into broader MG populations, including in seronegative patients, expected to start in 2024Update on pre-filled syringe development expected in first half of 2024; ongoing clinical studies expected to support potential approval in gMG and CIDP in 2024 Advancing Current Pipeline argenx continues to demonstrate breadth and depth within its immunology pipeline and is advancing multiple pipeline-in-a-product candidates. With efgartigimod, argenx is solidifying its leadership in FcRn and is on track to be approved or in development in 15 autoimmune indications by 2025. Beyond efgartigimod, argenx is advancing its earlier stage pipeline programs, including empasiprubart (C2 inhibitor) with Phase 2 studies ongoing in multifocal motor neuropathy (MMN), delayed graft function (DGF) and dermatomyositis (DM). In addition, argenx is evaluating ARGX-119, a muscle-specific kinase (MuSK) agonist in both congenital myasthenic syndrome (CMS) and amyotrophic lateral sclerosis (ALS). Evaluation ongoing to determine path forward in BALLAD study evaluating efgartigimod in bullous pemphigoid (BP), with an update expected in 2024Topline data from Phase 2 RHO study evaluating efgartigimod in primary Sjogren’s syndrome expected in first half of 2024Topline data from Phase 2 ALPHA study evaluating efgartigimod in post-COVID-19 postural orthostatic tachycardia syndrome (PC-POTS) expected in first half of 2024Topline data from seamless Phase 2/3 ALKIVIA study evaluating efgartigimod across three myositis subsets (immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and DM) expected in second half of 2024Full Phase 2 topline data from ARDA study evaluating empasiprubart in MMN expected to be shared in 2024; cohort 2 is ongoing to determine dose response ahead of Phase 3 study startPhase 1 study of ARGX-119 ongoing in healthy volunteers; subsequent Phase 1b/2a trials planned to assess early signal detection in patients with CMS and ALS in 2024 Leveraging Repeatable Innovation Playbook to Drive Long-Term Pipeline Growth argenx continues to invest in its discovery engine, the Immunology Innovation Program (IIP), to drive long-term sustainable pipeline growth. Through the IIP, four new pipeline candidates have been nominated, including: ARGX-213 targeting FcRn and further solidifying argenx’s leadership in this new class of medicine; ARGX-121 and ARGX-220, which are first-in-class targets broadening argenx’s focus across the immune system; and ARGX-109, targeting IL-6, which plays an important role in inflammation. On track to file four investigational new drug (IND) applications by end of 2025Received $30M milestone from AbbVie for advancement of ABBV-151 (ARGX-115) to Phase 2 FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL RESULTS argenx SE UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF PROFIT OR LOSS Three Months Ended December 31, Twelve Months Ended December 31, (in thousands of $ except for shares and EPS) 2023 2022 2023 2022Product net sales $374,351 $173,396 $1,190,783 $400,720Collaboration revenue 32,486 764 35,533 10,026Other operating income 11,003 7,956 42,278 34,520Total operating income $417,840 $182,116 $1,268,594 $445,267 Cost of sales $(39,477) $(12,786) $(117,835) $(29,431)Research and development expenses (306,373) (147,798) (859,492) (663,366)Selling, general and administrative expenses (208,826) (135,287) (711,905) (472,132)Loss from investment in joint venture (1,788) (677) (4,411) (677)Total operating expenses (556,464) (296,548) (1,693,643) (1,165,607) Operating loss $(138,624) $(114,432) $(425,049) $(720,341) Financial income $40,308 $13,925 $107,386 $27,665Financial expense (280) (990) (906) (3,906)Exchange gains/(losses) 37,418 60,259 14,073 (32,732) Loss for the period before taxes $(61,178) $(41,238) $(304,496) $(729,314)Income tax benefit / (expense) $(37,994) $2,625 $9,443 $19,720Loss for the period $(99,172) $(38,613) $(295,053) $(709,594)Loss for the year attributable to: Owners of the parent $(99,172) $(38,613) $(295,053) $(709,594)Weighted average number of shares outstanding 59,118,827 55,364,124 57,169,253 54,381,371Basis and diluted (loss) per share (in $) (1.68) (0.70) (5.16) (13.05)Net increase/(decrease) in cash, cash equivalents and current financial assets compared to year-end 2022 and 2021 $987,296 $(144,180)Cash and cash equivalents and current financial assets at the end of the period $3,179,844 $2,192,548 DETAILS OF THE FINANCIAL RESULTS Total operating income for the fourth quarter and full year in 2023 was $418 million and $1,269 million, respectively, compared to $182 million and $445 million for the same periods in 2022, and mainly consists of: Product net sales of VYVGART and VYVGART SC for the fourth quarter and full year in 2023, were $374 million and $1,191 million, respectively, compared to $173 million and $401 million for the same periods in 2022.Collaboration revenue for the fourth quarter and full year in 2023 was $32 million and $36 million, respectively, compared to $1 million and $10 million for the same periods in 2022. The increase is mainly related to the clinical development milestone argenx achieved with AbbVie following the dosing of the first patient in the Phase 2 trial for ABBV-151. Collaboration revenue for full year in 2023 also includes $1 million in royalty revenue from VYVGART sales in China.Other operating income for the fourth quarter and full year in 2023 was $11 million and $42 million, respectively, compared to $8 million and $35 million for the same periods in 2022. The other operating income for the fourth quarter and full year in 2023, primarily relates to research and development tax incentives and payroll tax rebates. Total operating expenses for the fourth quarter and full year in 2023 were $556 million and $1,694 million, respectively, compared to $297 million and $1,166 million for the same periods in 2022, and mainly consists of: Cost of sales for the fourth quarter and full year in 2023 was $39 million and $118 million, respectively, compared to $13 million and $29 million for the same periods in 2022. The cost of sales was recognized with respect to the sale of VYVGART and VYVGART SC.Research and development expenses for the fourth quarter and full year in 2023 were $306 million and $859 million, respectively, compared to $148 million and $663 million for the same periods in 2022. The research and development expenses mainly relate to external research and development expenses and personnel expenses incurred in the clinical development of efgartigimod in various indications and the expansion of other clinical and preclinical pipeline candidates. The research and development expenses for the fourth quarter and the full year in 2023, includes the amortization of the priority review voucher submitted with the sBLA filling for VYVGART Hytrulo for the treatment of CIDP, which resulted in an expense of $102 million.Selling, general and administrative expenses for the fourth quarter and full year in 2023 were $209 million and $712 million, respectively, compared to $135 million and $472 million for the same periods in 2022. The selling, general and administrative expenses mainly relate to professional and marketing fees linked to the commercialization of VYVGART and VYVGART SC, and personnel expenses. Financial income for the fourth quarter and full year in 2023 was $40 million and $107 million, respectively, compared to $14 million and $28 million for the same periods in 2022. The increase in financial income is mainly due to an increase in interest income which results from higher interest rates and a higher amount of current financial assets, cash and cash equivalents as a result of the financing round in July 2023. Exchange gains for the fourth quarter and full year in 2023 were $37 million and $14 million respectively, compared to $60 million of exchange gains and $33 million of exchange losses for the same periods in 2022. Exchange gains/losses are mainly attributable to unrealized exchange rate gains or losses on the cash, cash equivalents and current financial assets denominated in Euro. Income tax for the fourth quarter and full year in 2023 was $38 million of tax expense and $9 million of tax benefit, respectively, compared to $3 million and $20 million of tax benefit for the same periods in 2022. Tax expense for the fourth quarter in 2023, consists of $12 million of income tax benefit and $50 million of deferred tax expense, compared to $12 million of income tax expense and $15 million of deferred tax benefit for the comparable prior period. Net loss for the fourth quarter and full year in 2023, was $99 million and $295 million, respectively, compared to $39 million and $710 million over the prior year periods. On a per weighted average share basis, the net loss was $5.16 and $13.05 for the twelve months ended December 31, 2023 and 2022, respectively. Cash, cash equivalents and current financial assets totalled $3.2 billion as of December 31, 2023, compared to $2.2 billion as of December 31, 2022. The increase in cash and cash equivalents and current financial assets resulted primarily from the closing of a global offering of shares, including a U.S. offering, which resulted in the receipt of $1.2 billion in net proceeds in July 2023, partially offset by net cash flows used in operating activities. FINANCIAL GUIDANCE Based on its current operating plans, argenx expects its combined Research and development and Selling, general and administrative expenses in 2024 to be less than $2 billion. argenx expects to utilize up to $500 million of net cash in 2024 on these anticipated operating expenses as well as working capital and capital expenditures. EXPECTED 2024 FINANCIAL CALENDAR May 9, 2024: Q1 2024 financial results and business updateJuly 25, 2024: Q2 2024 financial results and business updateOctober 31, 2024: Q3 2024 financial results and business update CONFERENCE CALL DETAILS The full year 2023 financial results and fourth quarter business update will be discussed during a conference call and webcast presentation today at 2:30 pm CET/8:30 am ET. A webcast of the live call may be accessed on the Investors section of the argenx website at argenx.com/investors. A replay of the webcast will be available on the argenx website. Dial-in numbers: Please dial in 15 minutes prior to the live call. Belgium 32 800 50 201France 33 800 943355Netherlands 31 20 795 1090United Kingdom 44 800 358 0970United States 1 888 415 4250Japan 81 3 4578 9081Switzerland 41 43 210 11 32 About argenx argenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first approved neonatal Fc receptor (FcRn) blocker, globally in the U.S., Japan, Israel, the EU, the UK, China and Canada. The Company is evaluating efgartigimod in multiple serious autoimmune diseases and advancing several earlier stage experimental medicines within its therapeutic franchises. For more information, visit www.argenx.com and follow us on LinkedIn, Twitter, and Instagram. For further information, please contact: Media:Ben Petokbpetok@argenx.com Investors:Alexandra Roy (US)aroy@argenx.com Lynn Elton (EU)lelton@argenx.com Forward-looking Statements The contents of this announcement include statements that are, or may be deemed to be, “forward-looking statements.” These forward-looking statements can be identified by the use of forward-looking terminology, including the terms “plans,” “aims,” “continues,” “anticipates,” “expects,” “will,” or “commitment” and include statements argenx makes concerning its utilization of its learnings and momentum from its gMG launch for a potential CIDP approval and to position VYVGART SC for success; its plans to expand its patient reach, including through its multidimensional expansion efforts aimed at including patients earlier in the MG treatment paradigm and pursuing global regulatory approvals for MG as well as additional autoimmune indications; our goal to translate the ADHERE data into potential benefit for patients; the advancement of, and anticipated clinical development, data readouts and regulatory milestones and plans, including: (1) expected decisions on regulatory approvals of VYVGART for gMG in Switzerland, Australia, Saudi Arabia and South Korea by end of 2024, (2) expected decisions on approval of VYVGART SC for gMG in China through Zai Lab by end of 2024, (3) expected decisions on approval of VYVGART for ITP in Japan in the first quarter of 2024, (4) expected regulatory submissions of VYVGART SC of CIDP in Japan, Europe, China and Canada in 2024, (5) the expansion of our VYVGART registrational studies into broader MG populations, including in seronegative patients, expected to start in 2024, (6) the update on pre-filled syringe development expected in the first half of 2024, (7) clinical studies expected to support potential approval in gMG and CIDP in 2024, (8) expected update on the path forward for BALLAD study in 2024, (9) expected topline data from Phase 2 RHO in the first half of 2024, (10) expected topline data from Phase 2 ALPHA study in the first half of 2024, (11) expected topline data from Phase 2/3 ALKIVIA in the second half of 2024, (12) the full Phase 2 topline data from ARDA study expected in 2024, (13) planned Phase 1b/2a clinical trials of ARGX-119 in 2024, (14) four IND applications expected to be filed by end of 2025, (15) expected data from six Phase 2 proof-of-concept trials by the end of 2024, and (16) the expected approval or development in 15 autoimmune indications by 2025; the potential of its continued investment in its IIP to drive long-term sustainable pipeline growth; its future financial and operating performance, including its anticipated operating expenses and utilization of net cash for 2024; and our goal of translating immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. argenx’s actual results may differ materially from those predicted by the forward-looking statements as a result of various important factors, including but not limited to, the results of argenx’s clinical trials, expectations regarding the inherent uncertainties associated with development of novel drug therapies, preclinical and clinical trial and product development activities and regulatory approval requirements, the acceptance of our products and product candidates by our patients as safe, effective and cost-effective, and the impact of governmental laws and regulations on our business. A further list and description of these risks, uncertainties and other risks can be found in argenx’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in argenx’s most recent annual report on Form 20-F filed with the SEC as well as subsequent filings and reports filed by argenx with the SEC. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. argenx undertakes no obligation to publicly update or revise the information in this press release, including any forward-looking statements, except as may be required by law.