Inotersen sodium

WAINUATM U.S. launch progressing well; approved in UK; positive CHMP opinion Olezarsen FCS PDUFA December 19, 2024 Donidalorsen HAE PDUFA August 21, 2025; EU regulatory submission in process On track to achieve 2024 P&L financial guidance; increased 2024 cash guidance CARLSBAD, Calif., Nov. 6, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company") today reported financial results for the third quarter of 2024. "Today, we stand on the cusp of a new era for Ionis, with our first co-commercialization launch proceeding well with WAINUA, our first planned independent launch fast approaching and continued strong progress across our rich pipeline. With an upcoming December FDA action date, we are ready to independently bring olezarsen to people with familial chylomicronemia syndrome, a serious rare disease with no approved treatments in the U.S. We are similarly well positioned for our second independent launch for donidalorsen, which we believe could become a preferred treatment choice for people with hereditary angioedema, with an FDA action date of August 21, 2025," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "In parallel, we are making great progress across the rest of our rich Phase 3 pipeline. We expect Phase 3 results supporting olezarsen's second indication in severe hypertriglyceridemia and pelacarsen in Lp(a)-driven cardiovascular disease next year, as well as Phase 3 results supporting eplontersen's second indication in ATTR cardiomyopathy in the second half of 2026. We are also advancing our next wave of potentially transformational wholly owned medicines, including ION582 for Angelman syndrome, which we expect to enter Phase 3 development in the first half of next year following our positive end of Phase 2 discussion with the FDA. Our recent achievements, together with our advancing and expanding pipeline, position Ionis to deliver on our goal to bring a steady cadence of transformational medicines to people with serious diseases." Third Quarter 2024 Summary Financial Results(1): Financial Highlights Revenue for the three and nine months ended September 30, 2024 decreased by 7% and increased by 3% compared to the same periods last year, respectively. Ionis continued to generate revenue from diverse sources, including a new source of royalty revenue with the launch of WAINUA in the U.S in the first quarter Operating expenses for the three and nine months ended September 30, 2024 increased as planned compared to the same periods last year, excluding certain one-time costs in 2023, reflecting continued investments in late-stage development, including WAINUA for ATTR cardiomyopathy (ATTR-CM) and olezarsen for severe hypertriglyceridemia (sHTG), and commercialization efforts for WAINUA, olezarsen and donidalorsen Reaffirmed 2024 P&L financial guidance, increased cash guidance to $2.2 billion reflecting proceeds from equity offering Recent Marketed Medicines Highlights WAINUA (WAINZUA in Europe) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) achieved multiple commercial and regulatory milestones: Generated sales of $23 million and $44 million resulting in royalty revenue of $5 million and $10 million in the three and nine months ended September 30, 2024, respectively Received positive Committee for Medicinal Products for Human Use (CHMP) opinion from European Medicines Agency (EMA) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy Approved in UK by the Medicines and Healthcare products Regulatory Agency (MHRA) with an accelerated National Institute for Health and Care Excellence (NICE) recommendation; earning $30 million from AstraZeneca Launch underway in Canada, following approval and reimbursement from Health Canada SPINRAZA® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $381 million and $1.2 billion resulting in royalty revenue of $57 million and $152 million in the three and nine months ended September 30, 2024, respectively Positive Phase 2/3 DEVOTE study data presented from higher dose nusinersen; global regulatory applications planned QALSODY® (tofersen) granted marketing approval in China for the treatment of SOD1-ALS Recent Late-Stage Pipeline Highlights Olezarsen positioned to potentially treat two patient populations with urgent unmet need, familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG): NDA for patients with FCS under FDA Priority Review with a PDUFA date of December 19, 2024 Marketing authorization application (MAA) under regulatory review by the EMA Ongoing pivotal development program for sHTG on track for data in H2:2025 Donidalorsen Phase 3 data position it to potentially launch next year as the first RNA-targeted prophylactic treatment for people with hereditary angioedema (HAE): FDA accepted the NDA for patients with HAE with a PDUFA date of August 21, 2025; Otsuka, Europe and Asia Pacific partner, preparing to submit MAA Presented positive Phase 2 open label extension (OLE) study data in patients treated up to three years with every four weeks or every eight weeks dosing Zilganersen Phase 3 study fully enrolled as a potential treatment for Alexander disease; on track for data in 2025 Granted Fast Track designation by the FDA ION582 achieved important clinical and regulatory milestones enabling initiation of Phase 3 development in Angelman syndrome (AS) in H1:2025: Presented positive Phase 1/2 data in patients with AS at Angelman Syndrome Foundation (ASF) Family Conference Completed positive End-of-Phase 2 discussion with FDA, included alignment on Phase 3 design Reported positive data from the Phase 2 study of IONIS-FB-LRx in patients with immunoglobulin A nephropathy (IgAN); Roche continues to advance IONIS-FB-LRx in the Phase 3 IMAGINATION study Recent Other Pipeline Updates Sapablursen for the treatment of polycythemia vera granted orphan drug designation by FDA; enrollment complete in Phase 2 IMPRSSION study with data expected in 2025 IONIS-MAPTRx (BIIB080) enrollment complete in Phase 2 CELIA study in patients with early Alzheimer's disease (AD); data expected in 2026 Initiated first in human studies with multiple medicines from neurological disease pipeline: Phase 1/2 Orbit study of ION356 (PLP1) in patients with Pelizaeus-Merzbacher disease (PMD) Phase 1/2 HERO study of ION269 (APP), for the potential treatment of Alzheimer's disease (AD), which is initially being evaluated in patients with Down syndrome (DS) who have a genetic risk for developing AD Phase 1/2 ATTUNE study of ION440 (MECP2) in patients with MECP2 duplication syndrome Third Quarter 2024 Financial Results "This year has been marked by strong delivery on our pipeline and business goals, which position Ionis to deliver on our vision of bringing a steady cadence of innovative medicines to patients in need. Fully realizing these significant opportunities requires substantial investment. As a result, we recently executed an equity offering that extends our cash runway, enabling us to continue to invest in the numerous attractive opportunities ahead of us, including our near-term commercial launches with multi-billion-dollar revenue potential and our rich late and mid-stage pipeline," said Elizabeth L. Hougen, chief financial officer of Ionis. "Looking beyond this year, we will continue to invest in go-to-market preparations for our planned olezarsen and donidalorsen launches. Additionally, with our increased confidence in the potential of WAINUA and olezarsen to address broader patient populations, we plan to scale our capabilities in line with the significant potential of these important medicines. At the same time, we are investing in our next wave of medicines, including pre-commercialization activities and Phase 3 development for ION582 for Angelman syndrome and zilganersen for Alexander disease. We expect our investments today will position Ionis for sustainable growth for years to come." Revenue Ionis' revenue was comprised of the following: Commercial revenue for the three and nine months ended September 30, 2024 included a new source of royalty revenue with the launch of WAINUA in the U.S. in late January 2024. Ionis' commercial revenue for the three and nine months ended September 30, 2024 and 2023 also included royalties from the net sales of QALSODY, which Biogen launched in the U.S. in the second quarter of 2023 and in the EU in the second quarter of 2024. SPINRAZA product sales for the three months ended September 30, 2024 compared to the same period last year increased slightly in the U.S. and decreased outside of the U.S. primarily due to an annual order from a single country that did not recur in 2024. R&D revenue was relatively consistent for the three months ended September 30, 2024 compared to the same period last year. R&D revenue increased for the nine months ended September 30, 2024 compared to the same period last year primarily due to the amortization of upfront payments from the new collaborations with Roche and Novartis that Ionis entered into during the second half of last year. In addition, license fees increased year over year as a result of new collaborations Ionis entered into during the second quarter of 2024, including the expanded donidalorsen licensing agreement with Otsuka, which now includes the Asia-Pacific region in addition to Europe. These increases were partially offset by the decrease in WAINUA joint development revenue, which decreased as development activities relating to ATTRv-PN wound down with the launch of WAINUA for this indication. Operating Expenses Ionis' operating expenses, excluding one-time costs associated with a lease exit in the third quarter of 2023, increased for the three and nine months ended September 30, 2024 compared to the same periods in 2023, consistent with expectations. SG&A expenses increased year over year primarily due to the launch of WAINUA in the U.S. and launch preparation activities for olezarsen and donidalorsen, including establishing the field team for olezarsen in the second quarter of 2024. R&D expenses were essentially flat for the three and nine months ended September 30, 2024 compared to the same periods last year as several late-stage studies have ended. Balance Sheet As of September 30, 2024, Ionis' cash, cash equivalents and short-term investments increased to $2.5 billion compared to $2.3 billion at December 31, 2023. In September 2024, Ionis issued 11.5 million shares of its common stock at a public offering price of $43.50 per share that generated gross proceeds of $500 million, before deducting underwriting discounts and commissions and other offering expenses payable by Ionis. The Company plans to continue deploying its capital resources toward growth opportunities, and projects to end 2024 with $2.2 billion in cash, cash equivalents and short-term investments. Ionis' working capital also increased over the same period primarily due to the Company's higher cash and short-term investments balance. As a result of Ionis' advancing pipeline that has delivered several positive data readouts, Ionis expects to make increased investments in the years ahead with the goal to realize the value of these opportunities, with a focus on its wholly owned late-stage and next wave of innovative medicines. Webcast Management will host a conference call and webcast to discuss Ionis' third quarter 2024 results at 11:30 a.m. Eastern time on Wednesday, November 6, 2024. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company's third quarter 2024 earnings slides click here. For more information about SPINRAZA and QALSODY, visit and , respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s). INDICATION for WAINUA™ (eplontersen) WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA™ (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram. Ionis' Forward-looking Statement This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2023, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUATM is a registered trademark of the AstraZeneca group of companies. Ionis Investor Contact: D. Wade Walke, Ph.DD. [email protected] 760-603-2331 Ionis Media Contact: Hayley Soffer [email protected] 760-603-4679 Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations. Key 2024 Value Driving Events(1) SOURCE Ionis Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

10月8日，渤健中国宣布，中国国家药品监督管理局附条件批准托夫生注射液（商品名：凯盛迪）用于治疗携带超氧化物歧化酶1（SOD1）基因突变的肌萎缩侧索硬化（ALS）成人患者。 图片来源：NMPA 官网 自此，其成为中国内地第二款上市的ASO药物，且两款ASO药物的适应症均集中于神经系统疾病。 ASO与神经系统疾病 一直以来，由于神经系统结构及调控的复杂性，使得领域内的新药研发尤为困难，虽然近年来，神经系统疾病的发病率与日俱增，领域内的药物研发投入也在逐步增加。 但据ABPI（英国制药工业协会）的一份报告显示，相较于全球38%的研发资金集中到肿瘤和免疫治疗领域，中枢神经系统（CNS）领域仅吸引了7%的资金，地位差距一目了然。 塔夫茨大学药物开发研究中心的研究数据显示，FDA 最终批准上市的CNS药物成功率不到非 CNS 药物批准率的一半（分别为 6.2% 和 13.3%）。而无论是在临床前还是临床阶段，中枢神经系统药物的失败率都高于非中枢神经系统药物。 这也是为何全球大型制药企业在CNS领域陆续折戟，如2018年，辉瑞宣布退出神经系统领域，并裁员300位；2019年安进结束了其神经科学研究和早期开发项目，并宣布关闭了专注于神经科学领域研究的Erl Wood研究中心。 更关键的是，曾经带领MNC无往不利的小分子、抗体新药，却在中枢神经系统疾病面前频频失利，原因主要有以下几点： 血脑屏障阻碍有关药物进入中枢神经系统，包括ASO。 绝大多数CNS疾病目前尚缺乏明确的致病机理。 部分适应症实验设计困难，缺乏可以对疾病进行可观量化和评估的疾病标志物，如早期的阿尔兹海默症、精神分裂症。 毒副作用大，需要综合评估收益，安全性永远是CNS疾病首要考量因素。 虽然，在数十年的研究下，目前CNS领域临床上已有数百种小分子、抗体药物用于神经系统疾病，如多奈哌齐与美金刚用于治疗阿尔茨海默病、卡马西平与拉莫三嗪用于治疗癫痫，但这些药物通常只能减缓症状，却并不能达到治愈CNS疾病的效果。 而以ASO为代表的小核酸疗法却另辟蹊径，绕过小分子、抗体药物靶向蛋白的困难，与蛋白质之前的pre-mRNA或mRNA序列特异性结合，从而调节靶mRNA及下游靶蛋白的表达。因此，理论上ASO疗法一方面相较小分子、抗体药物具有更高成药性可能，另一方面也有望针对神经系统疾病进行病因治疗，达到治愈效果。 数据来源：公开数据整理 目前，神经系统疾病已成为了ASO疗法最受关注的领域，在已上市的12款ASO疗法中，有8款的适应症均为神经系统疾病，在230款在研ASO疗法中则有74款新药的适应症选择神经系统疾病，占比32.17%（下图）。 数据来源：药智数据 阿尔茨海默症成新关注点 当然，虽说ASO已成为神经系统疾病的新药研究中的主导疗法，但在神经系统疾病的细分适应症上，其主攻的方向却也发生了变化，即逐渐由杜氏肌营养不良（DMD）等罕见神经系统疾病转向了阿尔兹海默症等神经退行性疾病。 数据显示，在神经系统ASO疗法中，已上市产品中近50%的产品获批适应症为杜氏肌营养不良，这主要由于早期ASO研发水平尚浅，加之DMD作为单基因遗传性疾病，致病基因相对明确，ASO较容易在该疾病领域上取得突破。 但随着在研ASO神经疗法的数量增多，越来越多神经系统疾病的致病机制被研究透彻，部分ASO疗法的适应症已逐渐脱离罕见病领域，转而集中于市场更大的神经退行性疾病，如帕金森、阿尔兹海默症、癫痫等。 表1.神经系统ASO疗法中的“非罕见病”类型 药品名称 靶点 在研适应症（总） 原研单位 全球最高阶段 ION-464 SNCA 帕金森病;帕金森型多系统萎缩 Ionis Pharmaceuticals Inc;渤健 临床Ⅱ期 BIIB-094 LRRK2 帕金森病 Ionis Pharmaceuticals Inc;渤健 临床Ⅱ期 ION-717 PRNP 朊病毒感染 Ionis Pharmaceuticals Inc 临床Ⅱ期 BIIB-080 MAPT 阿尔茨海默病;轻度阿尔茨海默病性痴呆;阿尔茨海默病引起的轻度认知障碍;轻度认知障碍 Ionis Pharmaceuticals Inc;渤健 临床Ⅱ期 NIO-752 MAPT 阿尔茨海默病;进行性核上性麻痹;早期阿尔茨海默病 诺华制药 临床Ⅰ期 BMD-001 miR-485-3p 阿尔茨海默病;帕金森病;肌萎缩侧索硬化;神经炎 Biorchestra Ltd 临床前 PRAX-080 PCDH19 癫痫 Praxis Precision Medicines Inc 临床前 PRAX-100 - 癫痫性脑病 Praxis Precision Medicines Inc 临床前 INT-2H10 - 内侧脑颞叶癫痫症 InteRNA Technologies BV 临床前 PRAX-090 SYNGAP1 癫痫 Praxis Precision Medicines Inc 临床前 ION-716 PRNP 朊病毒感染 Ionis Pharmaceuticals Inc 临床前 SNP-614 LRRK2 帕金森病 赛神医药有限公司 临床前 数据来源：药智数据 其中，帕金森、阿尔茨海默症以及癫痫是非罕见病ASO神经疗法中较为集中的领域，尤其是阿尔茨海默症，在全球老年化趋势愈发严峻之下，相关市场研究迅速兴起，有关数据推测2030年我国AD患者将接近2000万，用药市场规模将接近200亿元。 阿尔茨海默症：BIIB080 作为首款进入临床试验期的tau蛋白靶向治疗轻度AD的ASO药物，BIIB080主要是通过结合MAPTmRNA并诱导RNaseH介导其降解以减少tau蛋白生成。 与小分子、抗体药物不同，BIIB080不仅可以通过靶向微管相关蛋白tau（MAPT）mRNA，阻止tau蛋白的产生，从而在早期阿尔茨海默病患者中降低脑脊液中的可溶性tau蛋白含量，且首次实现了减少聚集的病理性tau蛋白的作用。 更关键的是，虽然BIIB080作为AD首款ASO疗法与仑卡奈单抗、donanemab、semorinemab等抗体药物在有效性上暂无明显差距（粗略估计），但ASO疗法一方面高特异性、高效性和长效性特点导致其与AD等慢病相性更佳（有望提供每半年或一年用药一次的新疗法），另一方面，BIIB080以安全性作为主要临床终点，也充分展示了BIIB080在安全性方面的优势。 目前，BIIB080的Ⅱ期临床试验正在进行，其改善轻度AD患者的疾病进行及认知功能的效果有待研究。 血脑屏障难挡ASO 纵然优势明显，但要想更广泛地将ASO疗法应用于神经系统疾病，仍存在诸多制约因素，其中如何建立ASO的特殊递送方式，使其可以选择性靶向脑组织、脊髓，或某种细胞，尤其是神经元特异性的ASO配体受体就是最大问题，即如何让ASO疗法更高效地通过“血脑屏障”。 因为，通常情况下只有分子量小于450Da的疏水性分子才能够穿越血脑屏障，这就导致几乎现阶段所有的ASO疗法在没有特殊递送方式的情况，根本无法穿越血脑屏障，更别说达到理想的有效性。 对此，在研ASO药物主要采取两种不同的开发思路： 一者是绕过血脑屏障，直接开发用于鞘内注射剂型的ASO药物，如Spinraza在不需要递送系统的情况下就可以进入中枢神经系统。 二者则是通过ASO药物的靶向性改造，使其即使在静脉或皮下注射的方式下也能更高效地通过血脑屏障。 两者对比之下，前些年应用较普遍的鞘内注射、鼻内注射对患者的侵袭性太强，且伴随局部药物浓度过高的风险，近年来已被众多研究机构所摒弃，继而选择通过靶向性改造，开发静脉注射也能穿透血脑屏障的ASO药物，如以下两者。 2023年，Biorchestra开发的BMD-001作为一种针对AD和ALS等神经退行性疾病的ASO药物，其采用公司专利的脑聚合物（Brainpolymer）包裹，使BMD-001穿过血脑屏障和小胶质细胞、星形胶质细胞和神经元的质膜，降低microRNA485-3p的过度表达，高效治疗神经炎症和神经变性。 2024年，Denali研究团队在Science上发表了其关于ASO疗法的最新研究，其使用专有的OTV平台，开发出一款通过静脉注射递送ASO药物的新方法，使灵长类动物的大脑暴露量比之前提高了1000多倍。 龙头企业技术优势显著 血脑屏障的突破并非朝夕之事，ASO疗法在神经系统领域的局限性也不止血脑屏障一项，如此多技术痛点，往往需要多方产业与药企的共同努力才行。但ASO神经疗法领域目前尚处于早期发展阶段，市场格局尚未完全构筑，龙头集中效应过于明显。这对行业而言既是好事，也不是好事。 数据显示，在目前拥有神经系统适应症的在研ASO疗法中，超过90%的相关管线均来自海外龙头企业，TOP5企业分别是Ionis（23条）、渤健（10条）、WAVE（7条）、Praxis（4条）、武田（4条）。 表2.ASO神经系统疗法管线TOP5 排序 原研企业 管线数量 1 Ionis 23 2 渤健 10 3 WAVE 7 4 Sarepta 5 5 Praxis 4 数据来源：药智数据 并且，在原研企业方面，我国在ASO疗法上的布局情况与海外差距明显，不仅仅是ASO整体布局管线数量不足，且大部分ASO疗法还多集中于感染、肿瘤领域，而神经系统疾病领域目前仅有神济昌华的SG-005与SG006两款新药，且均处于临床前阶段。 这也导致ASO疗法在神经系统疾病的分布呈现三种不同类型： 即丰富技术积累的头部Biotech企业占据了领域的绝对优势，例如Ionis在ASO神经系统领域的技术垄断情况。 渤健、武田等MNC企业通过与头部Biotech企业合作来重点运营，利用自身临床与商业化的优势，实现双赢。 至于底层Biotech，目前其在ASO神经系统领域的优势并不明显，且管线数量稀少、推进缓慢。 作为ASO疗法的绝对霸主，Ionis凭借超过三十年的研发和上市经验，已经建立了坚实的技术领先优势，并积极拓展ASO在各种疾病领域的应用潜力。其分子修饰与分子递送能力作为企业突出的核心竞争力，深度体现在旗下两大技术平台——核苷酸化学修饰技术平台与GalNAc LICA递送技术平台。 图片来源： 肽研社 通过两大技术的融合，Ionis新药开发效能得以大大提高。目前仅神经系统ASO疗法领域，既有4款新药属于Ionis，分别是tofersen、nusinersen sodium、eplontersen与inotersen。而在研新药领域，各公司广泛与百健、阿斯利康、诺华和GSK、渤健等多家跨国药企达成合作，几乎是统领了该领域全球的新药产出，管线聚焦于神经、心血管与病毒几大领域。 图片来源：Ionis官网 如果说Alnylam是研究小核酸行业中的绝对先驱，那么Ionis就是ASO细分领域绝对的霸主，几乎掌握着整个行业发展的趋势，甚至未来ASO在神经系统疾病的发展也主要决定于Ionis的选择。 但是，光靠一个龙头企业推动整个创新领域发展，明显力有不逮。要想整个领域快速发展，MNC与龙头技术企业的合作只是一方面，另一方面相对底层的Biotech企业也应从更聚焦、更细分领域上做出差异化，如此才能让ASO神经系统领域得到可持续且高效的发展。 小结 过去几十年，纵然明知神经系统疾病患者群体庞大，但限于领域内疾病发生发展的复杂性，以及药物无法高效穿透血脑屏障等技术局限，以至于各类神经系统疾病的新药研发非常困难且缓慢。 ASO疗法的出现，因其区别于传统小分子、抗体药物的优势，一方面为该领域的新药研发提供了新的思路，另一方面也让新药疗法可以在具备足够有效性的同时，可以兼顾神经药物安全性与顺应性。 如今，在市场方面，随着领域技术成熟之后，ASO的神经系统适应症正逐渐由罕见病转向市场空间更大的慢性病领域，如阿尔兹海默症、帕金森等，这也预示着由市场反向推动行业进步的机会已至，未来或许会有更多看重慢病市场的资本投入其中。 技术方面，随着Ionis为首的一众ASO龙头企业对于化学修饰与递送技术水平上涨，越来越多CNS疾病有了明确的致病机理，甚至连制衡ASO疗效多年的“血脑屏障”因素也正在逐渐被攻克。 或许，在不久的未来，至少在神经系统疾病领域，ASO疗法或许真能做到一家独大？ 来源 | 博药（药智网获取授权转载） 撰稿 | 头孢 责任编辑 | 八角 声明：本文系药智网转载内容，图片、文字版权归原作者所有，转载目的在于传递更多信息，并不代表本平台观点。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。 商务合作 | 王存星 19922864877（同微信）  阅读原文，是受欢迎的文章哦