Givosiran Sodium

Sep 09, 2025 CAMBRIDGE, Mass. --(BUSINESS WIRE)--Sep. 9, 2025-- Alnylam Pharmaceuticals, Inc. (“Alnylam”) (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today the pricing of its previously announced private offering of $575 million aggregate principal amount of 0.00% convertible senior notes due 2028 (the “notes”) to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the “Securities Act”). The size of the offering was increased from the previously announced offering of $500 million aggregate principal amount of notes. In addition, Alnylam granted the initial purchasers of the notes an option to purchase, for settlement within a 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $86.25 million aggregate principal amount of the notes. The offering is expected to close on September 12, 2025 , subject to customary closing conditions. The notes will be senior, unsecured obligations of Alnylam and will not bear regular interest, and the principal amount of the notes will not accrete. The notes will mature on September 15, 2028 , unless earlier converted, redeemed or repurchased. Before June 15, 2028 , noteholders will have the right to convert their notes in certain circumstances and during specified periods. From and after June 15, 2028 , noteholders may convert their notes at any time at their election until the close of business on the second scheduled trading day immediately before the maturity date. Alnylam will settle conversions by paying or delivering, as applicable, cash, shares of its common stock, par value $0.01 per share (“common stock”), or a combination of cash and shares of its common stock, at Alnylam’s election. The initial conversion rate is 1.4923 shares of common stock per $1,000 principal amount of the notes, which represents an initial conversion price of approximately $670.11 per share of Alnylam’s common stock. The initial conversion price represents a premium of approximately 40% above the U.S. composite volume weighted average price of Alnylam's common stock from 12:30 p.m. through 4:00 p.m. Eastern Daylight Time on September 9, 2025 , which was $478.6327 per share. The conversion rate and conversion price will be subject to adjustment upon the occurrence of certain events. The notes will be redeemable, in whole or in part (subject to certain limitations), for cash at Alnylam’s option at any time, and from time to time, on or after September 20, 2027 and on or before the 21st scheduled trading day immediately preceding the maturity date, if the last reported sale price per share of Alnylam’s common stock equals or exceeds 130% of the conversion price for a specified period of time. The redemption price will be equal to the principal amount of the notes to be redeemed, plus accrued and unpaid special interest, if any, to, but excluding, the redemption date. In connection with the pricing of the notes, Alnylam entered into privately negotiated capped call transactions with certain of the initial purchasers or their respective affiliates and certain other financial institutions (the “option counterparties”). The capped call transactions are expected generally to reduce potential dilution to Alnylam’s common stock upon conversion of any notes and/or offset any potential cash payments Alnylam is required to make in excess of the principal amount of converted notes, as the case may be, with such reduction and/or offset subject to a cap. The cap price of the capped call transactions will initially be approximately $837.61 per share of Alnylam’s common stock, which represents a premium of approximately 75% over the U.S. composite volume weighted average price of Alnylam’s common stock from 12:30 p.m. through 4:00 p.m. Eastern Daylight Time on September 9, 2025 . Alnylam has been advised that, in connection with establishing their initial hedges of the capped call transactions, the option counterparties or their respective affiliates expect to purchase shares of Alnylam’s common stock and/or enter into various derivative transactions with respect to Alnylam’s common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Alnylam’s common stock or the notes at that time. In addition, the option counterparties and/or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Alnylam’s common stock and/or purchasing or selling Alnylam’s common stock or other securities of Alnylam in secondary market transactions from time to time prior to the maturity of the notes (and are likely to do so during any observation period related to a conversion of notes or following certain repurchases or redemptions of the notes). This activity could cause or avoid an increase or a decrease in the market price of Alnylam’s common stock or the notes, which could affect the ability of holders to convert the notes and, to the extent the activity occurs following conversion or during any observation period related to a conversion of notes, it could affect the amount and value of the consideration that holders will receive upon conversion of such notes. Alnylam estimates that the net proceeds from the offering of the notes will be approximately $561.6 million (or approximately $645.9 million if the initial purchasers exercise their option to purchase additional notes in full), after deducting the initial purchasers’ discounts and estimated offering expenses payable by Alnylam . Alnylam intends to use approximately $30.7 million of the net proceeds from the offering to pay the cost of the capped call transactions. If the initial purchasers exercise their option to purchase additional notes, Alnylam expects to use a portion of the net proceeds from the sale of the additional notes to enter into additional capped call transactions. In addition, Alnylam intends to use the remainder of the net proceeds from the offering, together with cash on hand, to repurchase for cash approximately $637.8 million aggregate principal amount of Alnylam’s 1.00% convertible senior notes due 2027 (the “existing notes”) through privately negotiated transactions entered into concurrently with the pricing of the notes. Concurrently with the pricing of the notes, Alnylam entered into privately negotiated transactions (the “note repurchase transactions”) with certain holders of the existing notes to repurchase for cash approximately $637.8 million aggregate principal amount of the existing notes for a total repurchase cost (including accrued and unpaid interest) of approximately $1,105.8 million . The terms of the note repurchase transactions were individually negotiated with certain holders of the existing notes and depended on a variety of factors, including the market price of Alnylam’s common stock and the trading price of the existing notes at the time of the note repurchase transactions. This press release is not an offer to repurchase the existing notes, and the offering of the notes is not contingent upon the repurchase of the existing notes. In connection with the note repurchase transactions, Alnylam expects that holders of the existing notes who have agreed to have their existing notes repurchased and who have hedged their equity price risk with respect to such existing notes (the “hedged holders”) will unwind all or part of their hedge positions by buying Alnylam’s common stock and/or entering into or unwinding various derivative transactions with respect to Alnylam’s common stock. The amount of Alnylam’s common stock to be purchased by the hedged holders or the notional number of shares of Alnylam’s common stock underlying such derivative transactions may be substantial in relation to the historic average daily trading volume of Alnylam’s common stock. This activity by the hedged holders could increase (or reduce the size of any decrease in) the market price of Alnylam’s common stock, including concurrently with the pricing of the notes, resulting in a higher effective conversion price of the notes. Alnylam cannot predict the magnitude of such market activity or the overall effect it will have on the price of the notes or Alnylam’s common stock and the corresponding effect on the initial conversion price of the notes. The notes were offered only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act. The offer and sale of the notes and any shares of common stock issuable upon conversion of the notes have not been, and will not be, registered under the Securities Act or any other securities laws, and the notes and any such shares cannot be offered or sold absent registration or except pursuant to an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and any other applicable securities laws. This press release does not constitute an offer to sell, or the solicitation of an offer to buy, the notes or any shares of common stock issuable upon conversion of the notes, nor will there be any sale of the notes or any such shares, in any state or other jurisdiction in which such offer, sale or solicitation would be unlawful. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products include AMVUTTRA® (vutrisiran), ONPATTRO® (patisiran), GIVLAARI® (givosiran), and OXLUMO® (lumasiran), which are being developed and commercialized by Alnylam , and Leqvio® (inclisiran) and Qfitlia™ (fitusiran), which are being developed and commercialized by Alnylam’s partners, Novartis and Sanofi, respectively. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. Alnylam Forward Looking Statements Various statements in this release concerning Alnylam’s future expectations, plans and prospects, including, without limitation, statements regarding: whether Alnylam will issue the notes; whether the note repurchase transactions will settle; the anticipated use of the net proceeds from the offering; expectations regarding the effect of the capped call transactions; expectations regarding actions of the hedged holders, the option counterparties and their respective affiliates; and whether the capped call transactions will become effective, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to Alnylam’s ability to successfully execute on its “Alnylam P5x25” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates; or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products; the outcome of litigation; the potential risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”), as may be updated from time to time in Alnylam’s subsequent Quarterly Reports on Form 10-Q, and in other filings that Alnylam makes with the SEC . In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. View source version on businesswire.com: https://www.businesswire.com/news/home/20250909474901/en/ Alnylam Pharmaceuticals, Inc. Christine Akinc (Investors and Media) +1-617-682-4340 Josh Brodsky (Investors) +1-617-551-8276 Source: Alnylam Pharmaceuticals, Inc.

无论是从技术突破、临床价值，还是商业前景来看，小核酸药物都迎来了发展的黄金时代。 今年，受 RNAi 疗法 Amvuttra 销售表现远超预期等因素的带动，Alnylam 股价强势上扬 95%，市值也一举突破了 600 亿美元大关。而 Ionis 和 Avidity 等小核酸上市企业表现同样稳健，2025 年以来股价涨幅分别超过 50% 和 20%。 与此同时，凭借靶标选择广泛、治疗效果持久等独特优势，小核酸药物也正在成为投资机构和制药巨头眼中的下一个掘金高地。 据不完全统计，今年以来，国内已经有 8 家小核酸企业获得了融资，其中浩博医药、靖因药业、瑞博生物均完成了超 2 亿元融资。海外方面，诺华、礼来、艾伯维、赛诺菲等制药巨头亦通过交易并购不断加码小核酸赛道。 来源：Insight 数据库整理（仅统计 IPO 前融资） 资本和产业的竞相追逐，无疑佐证了小核酸药物巨大的市场潜力。小核酸药物已经来到商业爆发的前夜。 四十年沉浮，终获突破 小核酸赛道的发展，经历了长达四十年的技术沉淀和突破。 小核酸药物包括反义寡核苷酸（ASO）、小干扰 RNA（siRNA）、微小 RNA（miRNA）、适配体、抗体核酸偶联药物（AOC）等，它们主要通过碱基互补配对原则作用于细胞内的 mRNA，调节基因表达和蛋白质水平，从而发挥治疗作用。 早在 1978 年，Zamecnik 和 Stephenson 博士就提出了 ASO 的概念，但学术向产业转化过程总是充满困难的，直到 1998 年，全球首款 ASO 药物福米韦生才获 FDA 批准上市，用于治疗获得性免疫缺陷综合征患者并发的由巨细胞病毒引起的视网膜炎。可惜随着高效抗逆转录病毒疗法的发展，福米韦生市场需求严重萎缩，上市仅 4 年（2002 年）就在欧洲退市。 20 世纪 90 年代以来，RNA 适配体、miRNA、RNAi 先后被发现，进一步掀起了小核酸药物研发的热潮。然而，由于潜在免疫原性、递送系统缺乏等，小核酸药物研发进展始终缓慢，临床研究也屡屡受挫。2010 年，诺华和罗氏终止了与 Alnylam 的合作，随后辉瑞和雅培也放弃了 RNAi 项目的开发。制药巨头的先后离场，使得这个行业陷入停滞。 转折发生在 2014 年，Ionis 和 Alnylam 分别在期刊上发表了 N-乙酰半糖胺（GalNAc）-ASO 和 GalNAc-siRNA 偶联技术。这个递送系统的出现，让小核酸药物重新焕发出了生机。 GalNAc 是唾液酸受体（ASGPR）的靶向配体，具有高度肝脏靶向性，通过较低药物剂量便可实现长效，毒性较小。2019 年，首款 GalNAc-siRNA 药物 Givosiran 获 FDA 批准上市。2023 年 12 月，首款GalNAc-ASO 药物 Eplontersen 获 FDA 批准上市。 来源：Alnylam 公司官网 不过由于 ASGPR 仅在肝实质细胞特异性高表达，GalNAc 递送系统仍存在组织局限性。为拓展到更多疾病领域，小核酸企业还在不断验证新型递送平台，比如Alnylam 开发了能够靶向 CNS、 眼部和肺部的 C16 平台等。而得益于化学修饰和递送技术的革新，小核酸药物也开始进入收获期。 小核酸为何能成为新宠？ Insight 数据库显示，目前全球在研的小核酸新药已经超过 1200 款，其中获批上市的有 22 款（包含撤市的产品），包括 7 款 siRNA 药物、13 款 ASO 药物和 2 款适配体。 来源：Insight 数据库整理 从获批上市的产品来看，小核酸已经在罕见病适应症上率先获得突破，包括杜氏肌营养不良、脊髓性肌肉萎缩症、转甲状腺素蛋白淀粉样变性、血友病、家族性高乳糜微粒血症等，与此同时开始逐步拓展至慢性疾病适应症。 英克司兰钠（商品名：Leqvio）是全球首款用于降血脂的 siRNA 药物，2021 年 12 月首次在美国获批上市。与传统化药和单抗相比，该产品每半年注射一次便可达到良好的降低 LDL-C 效果。 英克司兰钠目前已经在中、美、日、欧等多个国家和地区斩获监管批准，由Alnylam 和诺华共同负责商业化。该产品自上市以来销售额一路突飞猛进，今年第二季度收入 2.98 亿美元，上半年合计收入 5.55 亿美元，有望成为新的重磅炸弹。 来源：华福证券 小核酸药物在慢性疾病领域的临床和商业价值得到验证，是药企和资本竞相涌入这个赛道的关键原因之一。根据 Insight 数据库，除高血脂外，目前小核酸药物在研适应症已广泛覆盖乙肝、痛风、IgA 肾病、代谢相关脂肪性肝炎（MASH）等疾病，这些均为患者基数庞大、临床需求长期未被充分满足的大适应症，商业前景广阔。 作为单抗、小分子后的第三大药物类型，小核酸的技术特性同样赋予了其不可替代的竞争优势。与传统药物相比，小核酸药物不仅研发周期更短，可靶向的分子范围更广，给药后疗效持续时间更长，研发成功率也更高。这些独特优势的叠加，进一步点燃了行业和资本布局小核酸赛道的热情。 Insight 数据库显示，近三年全球一共达成了近百起小核酸 BD 合作，交易金额也在逐年提升。尤其值得关注的是，今年刚刚过半，首付款金额就已经创下新高，这一鲜明的市场信号，正是小核酸药物临床价值与商业价值持续提升的直接印证。 来源：Insight 数据库（截至 8 月 21 日） 西方亮，东方也要亮 与海外相比，我国小核酸药物起步相对较晚，目前仅有 3 款产品上市，还都是进口新药，包括渤健和 Ionis 合作开发的诺西那生钠、托夫生，以及诺华和 Alnylam 合作开发的英克司兰钠。 尽管还未有本土产品上市，但我国小核酸赛道已经快速崛起，发展势头强劲。一方面，自 2024 年 1 月以来，瑞博生物、舶望医药、靖因药业等企业先后与海外药企达到了 BD 大单，合作对象不乏勃林格殷格翰、诺华等 MNC，交易金额最多的高达 50 亿美元。 另一方面，国产小核酸新药研发管线正在快速扩充，数量仅次于美国。目前，在研新药已经达到了 300 多款，进入临床阶段的也有 68 款。从技术类型来看，国内小核酸临床管线呈现出明显的单极主导特征——siRNA 疗法占据绝对主流，而 ASO、小激活 RNA、miRNA 等疗法仍较少，在研新药项目仅有个位数。 来源：Insight 数据库 在适应症的选择上，与海外率先突破罕见病不同，国内大部分小核酸企业直接将视线瞄向了心血管代谢、肝病、痛风等慢性疾病领域。比如国产进展最快的AHB-137 针对的适应症就是慢性乙肝。 来源：Insight 数据库 AHB-137 是浩博医药基于 Med-Oligo™ 平台开发的一款非偶联型 ASO 药物，正在开展慢性乙肝的 III 期临床。今年 5 月，浩博医药在欧洲肝病学会年会上首次披露了该产品 IIb 期临床的中期数据。 这项研究一共纳入了 64 名受试者，随机分组接受AHB-137 300 mg 24 周治疗和 16 周治疗。结果显示，在24周治疗组中，75% 受试者达到了主要终点，乙型肝炎表面抗原（HBsAg）水平低于定量下限（<0.05 IU/mL）以及乙型肝炎病毒（HBV）DNA 水平低于定量下限（<10 IU/mL）。在 16 周治疗组中，66% 受试者达到了这一主要终点。 在达到主要终点的受试者中，超过 80% 的受试者在治疗 12 周内实现了 HBsAg 的清除，并且在治疗结束时，24 周和 16 周组分别有 54% 和 33% 的受试者出现了乙肝表面抗体（anti-HBs）的血清转换。AHB-137 在两个治疗组中均表现出良好的耐受性和有效的安全性。 来源：Insight 数据库 面对乙肝这一庞大的市场，舶望制药、恒瑞医药、瑞博生物、正大天晴等国内药企都布局了小核酸药物。不过与 AHB-137 不同，它们开发的都是 GalNAc-siRNA 疗法，目前尚处于早期临床阶段（II 期和 I 期）。 事实上，放眼全球，在乙肝、高脂血症、高血压等慢性疾病领域的小核酸药物研发赛道上，我国都已展现出强大的竞争力。国内药企通过密集的管线布局和高效的临床推进，已经建立起全球前列的研发梯队。这种战略聚焦不仅贴合国内医疗需求的实际痛点，更在全球小核酸药物的应用版图中开辟出了差异化竞争赛道。 结语 在竞争激烈的创新药环境中，每个参与者都渴望成为第一个撞线的人。当 ADC 与 GLP-1 的热潮逐渐理性，小核酸正成为制药巨头与投资人眼中的下一座金矿。 封面来源：站酷海洛 免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。 编辑：月牙 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn