mRNA-4359

编者按：寡核苷酸药物已成为全球新药开发的重要热点，近年来在不同疾病多个领域获得快速应用。为帮助合作伙伴更高效地推动寡核苷酸药物从实验室走向临床，药明康德（603259）围绕寡核苷酸及其相关化学偶联药物构建了一体化解决方案，覆盖定制合成、共价连接、工艺开发以及CMC等关键环节，为寡核苷酸及复杂偶联药物的发现与开发提供有力支持。本文将盘点2026年第二季度寡核苷酸领域的重要进展，带您了解这一快速发展领域的最新动态与趋势。 监管进展 2026年第二季度，寡核苷酸疗法在代谢疾病、罕见病、神经系统疾病及慢性乙肝等领域迎来多项关键监管进展。在脂质代谢疾病领域，Ionis Pharmaceuticals旗下反义寡核苷酸（ASO）疗法Tryngolza（olezarsen）在6月获得美国FDA扩展适应症批准，作为饮食控制的辅助疗法，用于降低成人重度高甘油三酯血症（sHTG）患者的甘油三酯水平和急性胰腺炎风险。同月，Arrowhead Pharmaceuticals旗下siRNA疗法Redemplo（plozasiran）在欧盟获批，用于降低成人家族性乳糜微粒血症综合征（FCS）患者的甘油三酯水平。这两款获批疗法均靶向甘油三酯代谢的关键调节因子载脂蛋白C-III（apoC-III）。 神经系统疾病和罕见病方向也迎来监管推进。渤健（Biogen）旗下ASO疗法salanersen获得美国FDA突破性疗法认定，用于治疗脊髓性肌萎缩症（SMA）。根据新闻稿，salanersen旨在调节SMN2前体mRNA剪接，有望实现每年一次给药。Praxis Precision Medicines旗下ASO疗法elsunersen也在本季度获得美国FDA突破性疗法认定，用于治疗由SCN2A功能获得性变异导致的早发性发育性癫痫性脑病（SCN2A-DEE）相关癫痫发作。 在杜氏肌营养不良症（DMD）领域，Dyne Therapeutics本季度向美国FDA提交了z-rostudirsen的生物制品许可申请（BLA），用于治疗适合外显子51跳跃的DMD患者。Z-rostudirsen由磷酰二胺吗啉寡聚体（PMO）与靶向TfR1的抗体片段偶联而成。由于TfR1在肌肉组织中具有较高表达，这一设计旨在借助受体介导的递送机制，提高PMO进入相关组织和细胞的能力，并促进外显子51跳跃，从而产生近全长抗肌萎缩蛋白。此外，再生元（Regeneron Pharmaceuticals）与Alnylam Pharmaceuticals合作开发的皮下注射、补体C5靶向siRNA疗法cemdisiran也在本季度取得监管进展。该疗法用于治疗全身型重症肌无力（gMG）的监管申请已获美国FDA和欧洲药品管理局（EMA）受理，美国FDA还授予该申请优先审评资格，目标审评日期为2026年11月；欧盟委员会预计将在2027年下半年作出决定。 在慢性乙型肝炎（CHB）领域，美国FDA已受理Ionis与GSK联合开发的潜在“first-in-class”ASO药物bepirovirsen的新药申请（NDA），并授予其优先审评资格，该申请的PDUFA日期定为2026年10月26日。同时，该疗法也获得FDA突破性疗法认定。与此同时，Arbutus Biopharma旗下RNAi疗法imdusiran获得美国FDA快速通道资格，用于治疗慢性乙肝。 临床进展 在临床研究方面，2026年第二季度，寡核苷酸疗法向肝脏以外适应症拓展的趋势更加明显，相关探索已延伸至神经系统疾病、肌肉疾病、心血管疾病、肿瘤免疫，并覆盖RNA编辑等更广泛领域。 在肿瘤治疗领域，mRNA癌症疫苗持续取得随访和早期临床进展。BioNTech和基因泰克（Genentech）联合开发的个体化新抗原mRNA疫苗autogene cevumeran的早期研究结果显示，在8名对疫苗产生免疫应答的胰腺癌患者中，有7名（87.5%）在手术后4至6年时仍然存活。在可规模化的“现货型”（off-the-shelf）癌症疫苗方面，Moderna在本季度公布了旗下mRNA-4359联合抗PD-1抗体Keytruda（pembrolizumab）作为既往未经治疗的局部晚期或转移性黑色素瘤一线疗法的1/2期临床试验结果。数据显示，12例可评估患者的客观缓解率（ORR）达到83%，其中包括2例完全缓解（CR）和8例部分缓解（PR），疾病控制率（DCR）为92%。值得关注的是，无论患者基线PD-L1表达水平如何，研究中均观察到治疗应答，提示该疗法可能具有较广的潜在适用人群。 在心血管相关疾病方向，Kardigan旗下每月给药一次的血管紧张素原（AGT）靶向ASO疗法tonlamarsen也在急性重度高血压患者的2期研究中显示出生物标志物降低和血压改善趋势。从基线至接受tonlamarsen治疗后第20周，患者血浆AGT水平显著下降，门诊收缩压（oSBP）也出现具有临床意义的降低（-6.7 mmHg）。HAYA Therapeutics旗下候选疗法HTX-001用于治疗非阻塞性肥厚型心肌病（nHCM）的1期临床试验，已完成首个队列给药。HTX-001是一款靶向长链非编码RNA（lncRNA）WISPER的反义寡核苷酸疗法，旨在通过调控心脏成纤维细胞状态来治疗心脏纤维化。 罕见病和神经肌肉疾病仍是本季度寡核苷酸疗法临床进展最密集的领域之一。Entrada Therapeutics公布了ENTR-601-44在DMD患者中的1/2期ELEVATE-44-201研究首个队列积极结果。该药物是一款旨在促进外显子44跳跃的在研寡核苷酸疗法。公司新闻稿显示，研究观察到外显子跳跃和抗肌萎缩蛋白表达增加，支持进一步推进后续剂量队列。诺华（Novartis）则在6月公布，其在研抗体偶联寡核苷酸药物（AOC）del-brax在1/2期研究的生物标志物队列中达到主要终点和关键次要终点。KHDC1L（cDUX）和肌酸激酶生物标志物水平的下降表明，在面肩肱型肌营养不良症（FSHD）患者中，该疗法既实现了强有力的靶点结合，也减少了肌肉损伤。基于这一结果，诺华将继续推进del-brax的3期研究。作为诺华通过收购Avidity Biosciences纳入其神经科学管线的三款潜在“first-in-class”疾病修饰AOC疗法之一，del-brax也进一步体现出AOC技术在神经肌肉疾病领域的开发潜力。 此外，多种新型RNA治疗策略也在本季度继续向临床验证迈进。Alltrna宣布AP003获准启动首次人体临床试验，公司称其为首款进入临床阶段的tRNA疗法。礼来（Eli Lilly and Company）公布了VERVE-102的早期临床数据。该疗法通过GalNAc偶联脂质纳米颗粒（LNP）递送编码腺嘌呤碱基编辑器的mRNA和靶向PCSK9的引导RNA（gRNA），旨在通过一次给药实现对肝脏PCSK9基因的持久关闭。新闻稿指出，在最高剂量组中，单次给药后PCSK9最高下降88%，LDL-C最高下降62%；部分受试者随访时间最长达到18个月，仍观察到持久疗效，支持其作为高胆固醇血症一次性治疗方案的潜力。Wave Life Sciences旗下RNA编辑寡核苷酸（AIMer）疗法WVE-006则在α-1抗胰蛋白酶缺乏症（AATD）相关研究中取得积极进展。RestorAATion-2试验数据显示，单次给予WVE-006即可使循环中的突变型Z-AAT较基线出现强效、剂量依赖性下降，降幅最高可达59.1%（600 mg）。该试验结果也推动公司与FDA讨论潜在加速批准路径。 研发合作与融资进展 在产业合作与融资方面，2026年第二季度，多项围绕RNAi管线与平台的合作相继达成。5月，Arrowhead Pharmaceuticals与Madrigal Pharmaceuticals达成全球独家许可协议，后者将获得ARO-PNPLA3的开发、生产和商业化权益。ARO-PNPLA3是一款靶向PNPLA3的临床阶段siRNA疗法，拟用于治疗携带PNPLA3 I148M变异的代谢功能障碍相关脂肪性肝炎（MASH）患者。根据协议，Madrigal将向Arrowhead支付2500万美元首付款，Arrowhead还有资格获得最高9.75亿美元的开发、监管及销售里程碑付款。同月，GSK与时安生物（SiranBio）就SA030达成一项潜在总额最高达10.05亿美元的全球独家许可协议。SA030是一款靶向ALK7的长效siRNA药物，已进入1期临床试验，用于治疗代谢与心血管疾病。 围绕RNAi平台的合作与资本支持也持续升温。Alnylam与Inceptive达成一项潜在总额最高达20亿美元的人工智能（AI）战略合作。双方计划将Alnylam在RNAi领域的研发平台和20余年专有siRNA数据，与Inceptive的基础模型和AI能力相结合，用于加速RNAi疗法发现和寡核苷酸设计。与此同时，City Therapeutics完成9950万美元B轮融资，所得资金将用于推进其RNAi工程平台和管线项目，包括正在开展1期临床试验的CITY-FXI，以及计划于2026年底前进入临床的另外两个项目。 在ASO领域，Ionis与Recordati就zilganersen达成美国以外地区的授权合作。Zilganersen是一款用于治疗亚历山大病（AxD）的在研ASO疗法，其新药申请已获美国FDA受理，并被授予优先审评资格，PDUFA日期为2026年9月22日。 本季度，靶向递送平台开发也取得多项进展。Vivatides Therapeutics完成超额认购的5400万美元A轮融资，所得资金将用于推进其肝外RNA靶向治疗平台和多个管线项目进入临床开发。该公司构建了差异化的肝外递送平台，覆盖siRNA和ASO两类技术路线，并在配体偶联、递送效率、组织靶向特异性及安全性等方面取得重要进展。Interna Therapeutics与第一三共（Daiichi Sankyo）达成研究合作，双方将评估Interna分子纳米马达（Molecular Nano Motor，MNM）技术作为靶向治疗递送增强工具的应用潜力。MNM平台旨在实现多种治疗载荷的高效细胞内递送，包括siRNA、反义寡核苷酸、多肽及其他大分子，且无需依赖传统递送系统。通过增强药物进入细胞的能力和组织穿透性，MNM有望提升多种适应症中靶向治疗的疗效。 这些进展也表明，递送体系正在成为寡核苷酸疗法进一步突破适应症边界的关键环节。无论是siRNA、ASO、mRNA，还是RNA编辑等新型治疗模式，如何将治疗载荷高效、稳定并可规模化地递送至目标组织和细胞，正越来越成为决定项目临床转化和后续产业化的重要因素。因此，在递送技术持续创新的同时，能够支持脂质材料研发、LNP制剂开发、工艺放大和CMC生产的一体化平台能力，也在RNA药物开发中发挥着越来越重要的作用。 在LNP递送体系快速发展的背景下，脂质材料的研发与合成能力正成为寡核苷酸药物研发的重要基础。药明康德旗下合全药业（WuXi STA）的脂质纳米颗粒平台旨在帮助客户项目从研发阶段快速推进到临床和商业化生产阶段。 平台的LNP研发实验室配备了多通道微混合系统、不同规模的切向流过滤（TFF）系统、无菌过滤系统和分析设备。并且配备其它混合技术与设备，例如MIVM、微流体、精密纳米系统和LNP挤出系统。研发实验室可进行LNP可行性研究、制剂开发和工艺开发。 平台的LNP生产车间为模块化设计，将多通道芯片、微混合系统和复杂的制备系统整合到一个以多通道微混合器为核心的LNP生产平台中，在药物载量、脂质体粒径控制和包封效率方面有显著的优势。此外，模块化设计提供了更高的灵活性，使该平台能够支持各种生产规模，每批可达10-50升。 值得一提的是，合全药业也可以提供寡核苷酸和特定功能性脂质（如可电离脂质和聚乙二醇化脂质）的合成和生产服务。该平台提供端到端服务，包含原料药、制剂和分析支持的一体化CMC开发和生产服务。同时，药明康德旗下WuXi TIDES团队全面掌握多种偶联位点与修饰技术，针对siRNA、ASO等不同类型开发出超过20种可供偶联的脂质类型，并在酰胺偶联、点击化学等多种偶联技术上积累了丰富实操经验。 总体来看，2026年第二季度寡核苷酸疗法行业延续了较高活跃度。一方面，脂质代谢疾病、慢性乙肝、神经系统疾病、罕见病和自身免疫疾病等适应症迎来多项监管推进；另一方面，肝外递送和非肝脏适应症拓展成为临床开发的重要趋势，相关探索已延伸至肿瘤免疫、心血管疾病、神经肌肉疾病、RNA编辑和tRNA疗法等更广泛领域。与此同时，抗体偶联寡核苷酸、GalNAc偶联脂质纳米颗粒、RNA编辑寡核苷酸以及分子纳米马达等新型递送和治疗策略，正在不断拓展寡核苷酸疗法的边界。随着更多关键临床研究、监管申请、授权合作和平台融资落地，寡核苷酸疗法正在从相对成熟的肝脏靶向应用，逐步走向更多具有未满足医疗需求的疾病治疗场景。 Q2 2026 Review of Oligonucleotide Drugs Oligonucleotide drugs have become an important focus in global new drug development and have seen rapid application across multiple therapeutic areas in recent years. To help partners advance oligonucleotide drugs from the laboratory to the clinic more efficiently, WuXi AppTec has built an integrated solution around oligonucleotides and related chemically conjugated drugs. The solution covers key areas including custom synthesis, covalent conjugation, process development, and CMC, providing strong support for the discovery and development of oligonucleotides and complex conjugated drugs. This article reviews key developments in the oligonucleotide field in the second quarter of 2026 and highlights the latest dynamics and trends in this rapidly evolving area. Regulatory Progress In the second quarter of 2026, oligonucleotide therapeutics achieved several key regulatory milestones across metabolic diseases, rare diseases, neurological disorders, and chronic hepatitis B. In lipid metabolism disorders, Ionis Pharmaceuticals’ antisense oligonucleotide (ASO) therapy Tryngolza (olezarsen) received approval for an expanded indication from the U.S. FDA in June as an adjunct to diet to reduce triglyceride levels and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG). In the same month, Arrowhead Pharmaceuticals’ siRNA therapy Redemplo (plozasiran) was approved in the European Union to reduce triglyceride levels in adults with familial chylomicronemia syndrome (FCS). Both approved therapies target apolipoprotein C-III (apoC-III), a key regulator of triglyceride metabolism. Neurological disorders and rare diseases also saw regulatory advances. Biogen’s ASO therapy salanersen received Breakthrough Therapy designation from the U.S. FDA for the treatment of spinal muscular atrophy (SMA). According to the company, salanersen is designed to modulate SMN2 pre-mRNA splicing and has the potential to enable once-yearly dosing. Praxis Precision Medicines’ ASO therapy elsunersen also received Breakthrough Therapy designation from the U.S. FDA during the quarter for the treatment of seizures associated with early-onset developmental and epileptic encephalopathy caused by SCN2A gain-of-function variants (SCN2A-DEE). In Duchenne muscular dystrophy (DMD), Dyne Therapeutics submitted a biologics license application (BLA) to the U.S. FDA during the quarter for z-rostudirsen, which is intended for patients with DMD amenable to exon 51 skipping. Z-rostudirsen consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to an antibody fragment targeting TfR1. As TfR1 is highly expressed in muscle tissue, this design aims to leverage receptor-mediated delivery to enhance PMO entry into relevant tissues and cells, promote exon 51 skipping, and thereby produce near full-length dystrophin. In addition, cemdisiran, a subcutaneously administered siRNA therapy targeting complement C5 and co-developed by Regeneron Pharmaceuticals and Alnylam Pharmaceuticals, also made regulatory progress during the quarter. Regulatory applications for cemdisiran in generalized myasthenia gravis (gMG) have been accepted by the U.S. FDA and the European Medicines Agency (EMA). The U.S. FDA also granted the application Priority Review, with a target action date in November 2026; a European Commission decision is expected in the second half of 2027. In chronic hepatitis B (CHB), the U.S. FDA accepted the new drug application (NDA) for bepirovirsen, a potential first-in-class ASO drug co-developed by Ionis and GSK, and granted it Priority Review. The PDUFA date for the application is set for October 26, 2026. The therapy has also received Breakthrough Therapy designation from the FDA. Meanwhile, Arbutus Biopharma’s RNAi therapy imdusiran received Fast Track designation from the U.S. FDA for the treatment of chronic hepatitis B. Clinical Progress In clinical development, the second quarter of 2026 further highlighted the growing trend of oligonucleotide therapeutics expanding beyond liver-targeted indications. Clinical exploration is now extending into broader areas, including neurological disorders, muscle diseases, cardiovascular diseases, cancer immunotherapy, and RNA editing. In oncology, mRNA cancer vaccines continued to make progress. Early study results for autogene cevumeran, an individualized neoantigen mRNA vaccine jointly developed by BioNTech and Genentech, showed that among eight pancreatic cancer patients who mounted an immune response to the vaccine, seven patients (87.5%) remained alive four to six years after surgery. In the field of scalable off-the-shelf cancer vaccines, Moderna also reported results during the quarter from a Phase 1/2 clinical trial of mRNA-4359 in combination with the anti-PD-1 antibody Keytruda (pembrolizumab) as a first-line therapy for previously untreated locally advanced or metastatic melanoma. Data showed that among 12 evaluable patients, the objective response rate (ORR) reached 83%, including two complete responses (CRs) and eight partial responses (PRs), while the disease control rate (DCR) was 92%. Notably, treatment responses were observed regardless of baseline PD-L1 expression, suggesting that the therapy may have potential applicability across a broad patient population. In cardiovascular-related diseases, Kardigan’s once-monthly angiotensinogen (AGT)-targeting ASO therapy tonlamarsen showed biomarker reduction and a trend toward blood pressure improvement in a Phase 2 study in patients with acute severe hypertension. From baseline to Week 20 after tonlamarsen treatment, patients’ plasma AGT levels decreased significantly, and office systolic blood pressure (oSBP) also showed a clinically meaningful reduction (-6.7 mmHg). HAYA Therapeutics’ pipeline HTX-001 has completed dosing of the first cohort in a Phase 1 clinical trial for the treatment of non-obstructive hypertrophic cardiomyopathy (nHCM). HTX-001 is an ASO therapy targeting the long non-coding RNA (lncRNA) WISPER and is designed to treat cardiac fibrosis by modulating the state of cardiac fibroblasts. Rare diseases and neuromuscular disorders remained among the most active areas for oligonucleotide clinical progress during the quarter. Entrada Therapeutics announced positive first-cohort results from the Phase 1/2 ELEVATE-44-201 study of ENTR-601-44 in patients with DMD. The investigational oligonucleotide therapy is designed to promote exon 44 skipping. According to the company’s press release, the study observed increased exon skipping and dystrophin expression, supporting advancement into subsequent dose cohorts. Novartis announced in June that its investigational antibody oligonucleotide conjugate (AOC) del-brax met the primary endpoint and key secondary endpoints in the biomarker cohort of a Phase 1/2 study. Reductions in KHDC1L (cDUX) and creatine kinase biomarkers indicate that, in patients with facioscapulohumeral muscular dystrophy (FSHD), the therapy achieved strong target engagement and reduced muscle damage. Based on these results, Novartis will continue to advance the Phase 3 study of del-brax. As one of three potential first-in-class disease-modifying AOC therapies added to Novartis’ neuroscience pipeline through its acquisition of Avidity Biosciences, del-brax further demonstrates the development potential of AOC technology in neuromuscular diseases. In addition, multiple novel RNA therapeutic strategies continued to move toward clinical validation during the quarter. Alltrna announced that AP003 was cleared to initiate its first-in-human clinical trial, and the company described it as the first tRNA therapy to enter clinical development. Eli Lilly and Company reported early clinical data for VERVE-102. The therapy uses GalNAc-conjugated lipid nanoparticles (LNPs) to deliver mRNA encoding an adenine base editor and guide RNA (gRNA) targeting PCSK9, with the goal of achieving durable silencing of the hepatic PCSK9 gene through a single administration. According to the company, in the highest-dose group, a single dose led to up to 88% reduction in PCSK9 level and up to 62% reduction in LDL-C. Some participants were followed for up to 18 months, with durable efficacy still observed, supporting its potential as a one-time treatment for hypercholesterolemia. Wave Life Sciences’ RNA editing oligonucleotide therapy WVE-006, an AIMer therapy, also made positive progress in studies related to alpha-1 antitrypsin deficiency (AATD). Data from the RestorAATion-2 trial showed that a single dose of WVE-006 resulted in a potent, dose-dependent reduction from baseline in circulating mutant Z-AAT, with reductions of up to 59.1% at 600 mg. These results also supported the company’s discussions with the FDA regarding a potential accelerated approval pathway. Partnerships and Financing In industry collaborations and financing, the second quarter of 2026 saw multiple agreements centered on RNAi pipelines and platforms. In May, Arrowhead Pharmaceuticals and Madrigal Pharmaceuticals entered into a global exclusive licensing agreement under which Madrigal will obtain the rights to develop, manufacture, and commercialize ARO-PNPLA3. ARO-PNPLA3 is a clinical-stage siRNA therapy targeting PNPLA3 and is intended for the treatment of patients with metabolic dysfunction-associated steatohepatitis (MASH) who carry the PNPLA3 I148M variant. Under the agreement, Madrigal will pay Arrowhead an upfront payment of $25 million, and Arrowhead is eligible to receive up to $975 million in development, regulatory, and sales milestone payments. In the same month, GSK and SiranBio entered into a global exclusive licensing agreement for SA030, with a potential total value of up to $1.005 billion. SA030 is a long-acting siRNA drug targeting ALK7 and has entered Phase 1 clinical trials for the treatment of metabolic and cardiovascular diseases. Collaboration and capital support around RNAi platforms also continued to gain momentum. Alnylam and Inceptive entered into a strategic artificial intelligence (AI) collaboration with a potential total value of up to $2 billion. The two companies plan to combine Alnylam’s RNAi R&D platform and more than 20 years of proprietary siRNA data with Inceptive’s foundation models and AI capabilities to accelerate RNAi therapeutic discovery and oligonucleotide design. Meanwhile, City Therapeutics completed a $99.5 million Series B financing, with proceeds to be used to advance its RNAi engineering platform and pipeline, including CITY-FXI, which is currently in a Phase 1 clinical trial, as well as two additional programs planned to enter the clinic by the end of 2026. In the ASO field, Ionis and Recordati entered into a licensing collaboration for zilganersen outside the United States. Zilganersen is an investigational ASO therapy for Alexander disease (AxD). Its new drug application has been accepted by the U.S. FDA and granted Priority Review, with a PDUFA date of September 22, 2026. Targeted delivery platform development also made several advances during the quarter. Vivatides Therapeutics completed an oversubscribed $54 million Series A financing, with proceeds to support the advancement of its extrahepatic RNA-targeted therapeutic platform and multiple pipeline programs into clinical development. The company has built a differentiated extrahepatic delivery platform covering both siRNA and ASO technology approaches and has made important progress in ligand conjugation, delivery efficiency, tissue-targeting specificity, and safety. Interna Therapeutics entered into a research collaboration with Daiichi Sankyo, under which the parties will evaluate the potential of Interna’s Molecular Nano Motor (MNM) technology as a delivery-enhancing tool for targeted therapeutic modalities. The MNM platform is designed to enable efficient intracellular delivery of multiple therapeutic payloads, including siRNA, antisense oligonucleotides, peptides, and other macromolecules, without relying on traditional delivery systems. By enhancing drug entry into cells and tissue penetration, MNM has the potential to improve the efficacy of targeted therapies across multiple indications. These developments also indicate that delivery systems are becoming a critical component for oligonucleotide therapeutics to further expand the boundaries of their indications. Whether for siRNA, ASO, mRNA, or emerging modalities such as RNA editing, the ability to deliver therapeutic payloads to target tissues and cells efficiently, stably, and at scale is increasingly becoming a key factor in determining clinical translation and future industrialization. Therefore, as delivery technologies continue to evolve, integrated platform capabilities that support lipid material R&D, LNP formulation development, process scale-up, and CMC production are playing an increasingly important role in RNA drug development. Against the backdrop of rapid development in LNP delivery systems, lipid material R&D and synthesis capabilities are becoming an important foundation for oligonucleotide drug development. WuXi STA, an integral part of WuXi AppTec, has established an integrated lipid nanoparticle (LNP) development and manufacturing platform designed to support RNA therapeutics programs from early development through clinical and commercial production. As LNP and liposomal delivery systems rapidly advance across modalities such as mRNA, siRNA, and other nucleic acid therapeutics, the ability to design, synthesize, and manufacture high-quality lipid materials has become a critical foundation for successful drug development. WuXi STA’s platform combines advanced formulation expertise with scalable manufacturing infrastructure to help partners efficiently translate innovative RNA medicines into clinical candidates. The dedicated LNP development laboratories are equipped with multi-channel micro-mixing systems, multiple scales of tangential flow filtration (TFF) systems, sterile filtration units, and comprehensive analytical instrumentation. In addition, the laboratories incorporate diverse mixing technologies and equipment, including MIVM systems, microfluidic platforms, precision nano systems, and LNP extrusion systems, enabling feasibility studies, formulation development, and process optimization for a wide range of nucleic acid delivery applications. To support seamless scale-up, WuXi STA operates a modular LNP manufacturing suite that integrates multi-channel chips, micro-mixing technologies, and complex preparation systems within a production platform centered on multi-channel micro-mixers. This design enables precise control of drug loading, particle size distribution, and encapsulation efficiency while providing the flexibility to accommodate a variety of production scales, with batch volumes typically ranging from 10 to 50 liters. Importantly, WuXi STA can also synthesize and manufacture oligonucleotides as well as functional lipids, including ionizable lipids and PEGylated lipids, further strengthening its capabilities in nucleic acid delivery systems. Through this end-to-end platform, WuXi STA provides integrated CMC services encompassing API development, formulation development, analytical support, and GMP manufacturing, helping global partners accelerate the development of RNA-based therapeutics from concept to clinic and beyond. At the same time, the WuXi TIDES team, part of WuXi AppTec, has developed comprehensive expertise in a wide range of conjugation sites and modification technologies. For different modalities such as siRNA and ASO, the team has developed more than 20 types of lipids available for conjugation and has accumulated extensive hands-on experience across multiple conjugation technologies, including amide coupling and click chemistry. Overall, the oligonucleotide therapeutics sector maintained a high level of activity in the second quarter of 2026. On one hand, multiple indications, including lipid metabolism disorders, chronic hepatitis B, neurological disorders, rare diseases, and autoimmune diseases, achieved important regulatory progress. On the other hand, extrahepatic delivery and expansion into non-liver indications have become important trends in clinical development, with exploration extending into broader areas such as cancer immunotherapy, cardiovascular diseases, neuromuscular disorders, RNA editing, and tRNA therapies. At the same time, new delivery and therapeutic strategies, including antibody oligonucleotide conjugates, GalNAc-conjugated lipid nanoparticles, RNA editing oligonucleotides, and Molecular Nano Motor technology, are continuing to expand the boundaries of oligonucleotide therapeutics. As more pivotal clinical studies, regulatory applications, licensing collaborations, and platform financings move forward, oligonucleotide therapeutics are advancing from relatively mature liver-targeted applications toward a broader range of disease areas with significant unmet medical needs.

编者按：寡核苷酸药物已成为全球新药开发的重要热点，近年来在不同疾病多个领域获得快速应用。为帮助合作伙伴更高效地推动寡核苷酸药物从实验室走向临床，药明康德围绕寡核苷酸及其相关化学偶联药物构建了一体化解决方案，覆盖定制合成、共价连接、工艺开发以及CMC等关键环节，为寡核苷酸及复杂偶联药物的发现与开发提供有力支持。本文将盘点2026年第二季度寡核苷酸领域的重要进展，带您了解这一快速发展领域的最新动态与趋势。 监管进展 2026年第二季度，寡核苷酸疗法在代谢疾病、罕见病、神经系统疾病及慢性乙肝等领域迎来多项关键监管进展。在脂质代谢疾病领域，Ionis Pharmaceuticals旗下反义寡核苷酸（ASO）疗法Tryngolza（olezarsen）在6月获得美国FDA扩展适应症批准，作为饮食控制的辅助疗法，用于降低成人重度高甘油三酯血症（sHTG）患者的甘油三酯水平和急性胰腺炎风险。同月，Arrowhead Pharmaceuticals旗下siRNA疗法Redemplo（plozasiran）在欧盟获批，用于降低成人家族性乳糜微粒血症综合征（FCS）患者的甘油三酯水平。这两款获批疗法均靶向甘油三酯代谢的关键调节因子载脂蛋白C-III（apoC-III）。 神经系统疾病和罕见病方向也迎来监管推进。渤健（Biogen）旗下ASO疗法salanersen获得美国FDA突破性疗法认定，用于治疗脊髓性肌萎缩症（SMA）。根据新闻稿，salanersen旨在调节SMN2前体mRNA剪接，有望实现每年一次给药。Praxis Precision Medicines旗下ASO疗法elsunersen也在本季度获得美国FDA突破性疗法认定，用于治疗由SCN2A功能获得性变异导致的早发性发育性癫痫性脑病（SCN2A-DEE）相关癫痫发作。 在杜氏肌营养不良症（DMD）领域，Dyne Therapeutics本季度向美国FDA提交了z-rostudirsen的生物制品许可申请（BLA），用于治疗适合外显子51跳跃的DMD患者。Z-rostudirsen由磷酰二胺吗啉寡聚体（PMO）与靶向TfR1的抗体片段偶联而成。由于TfR1在肌肉组织中具有较高表达，这一设计旨在借助受体介导的递送机制，提高PMO进入相关组织和细胞的能力，并促进外显子51跳跃，从而产生近全长抗肌萎缩蛋白。此外，再生元（Regeneron Pharmaceuticals）与Alnylam Pharmaceuticals合作开发的皮下注射、补体C5靶向siRNA疗法cemdisiran也在本季度取得监管进展。该疗法用于治疗全身型重症肌无力（gMG）的监管申请已获美国FDA和欧洲药品管理局（EMA）受理，美国FDA还授予该申请优先审评资格，目标审评日期为2026年11月；欧盟委员会预计将在2027年下半年作出决定。 在慢性乙型肝炎（CHB）领域，美国FDA已受理Ionis与GSK联合开发的潜在“first-in-class”ASO药物bepirovirsen的新药申请（NDA），并授予其优先审评资格，该申请的PDUFA日期定为2026年10月26日。同时，该疗法也获得FDA突破性疗法认定。与此同时，Arbutus Biopharma旗下RNAi疗法imdusiran获得美国FDA快速通道资格，用于治疗慢性乙肝。 临床进展 在临床研究方面，2026年第二季度，寡核苷酸疗法向肝脏以外适应症拓展的趋势更加明显，相关探索已延伸至神经系统疾病、肌肉疾病、心血管疾病、肿瘤免疫，并覆盖RNA编辑等更广泛领域。 在肿瘤治疗领域，mRNA癌症疫苗持续取得随访和早期临床进展。BioNTech和基因泰克（Genentech）联合开发的个体化新抗原mRNA疫苗autogene cevumeran的早期研究结果显示，在8名对疫苗产生免疫应答的胰腺癌患者中，有7名（87.5%）在手术后4至6年时仍然存活。在可规模化的“现货型”（off-the-shelf）癌症疫苗方面，Moderna在本季度公布了旗下mRNA-4359联合抗PD-1抗体Keytruda（pembrolizumab）作为既往未经治疗的局部晚期或转移性黑色素瘤一线疗法的1/2期临床试验结果。数据显示，12例可评估患者的客观缓解率（ORR）达到83%，其中包括2例完全缓解（CR）和8例部分缓解（PR），疾病控制率（DCR）为92%。值得关注的是，无论患者基线PD-L1表达水平如何，研究中均观察到治疗应答，提示该疗法可能具有较广的潜在适用人群。 在心血管相关疾病方向，Kardigan旗下每月给药一次的血管紧张素原（AGT）靶向ASO疗法tonlamarsen也在急性重度高血压患者的2期研究中显示出生物标志物降低和血压改善趋势。从基线至接受tonlamarsen治疗后第20周，患者血浆AGT水平显著下降，门诊收缩压（oSBP）也出现具有临床意义的降低（-6.7 mmHg）。HAYA Therapeutics旗下候选疗法HTX-001用于治疗非阻塞性肥厚型心肌病（nHCM）的1期临床试验，已完成首个队列给药。HTX-001是一款靶向长链非编码RNA（lncRNA）WISPER的反义寡核苷酸疗法，旨在通过调控心脏成纤维细胞状态来治疗心脏纤维化。 罕见病和神经肌肉疾病仍是本季度寡核苷酸疗法临床进展最密集的领域之一。Entrada Therapeutics公布了ENTR-601-44在DMD患者中的1/2期ELEVATE-44-201研究首个队列积极结果。该药物是一款旨在促进外显子44跳跃的在研寡核苷酸疗法。公司新闻稿显示，研究观察到外显子跳跃和抗肌萎缩蛋白表达增加，支持进一步推进后续剂量队列。诺华（Novartis）则在6月公布，其在研抗体偶联寡核苷酸药物（AOC）del-brax在1/2期研究的生物标志物队列中达到主要终点和关键次要终点。KHDC1L（cDUX）和肌酸激酶生物标志物水平的下降表明，在面肩肱型肌营养不良症（FSHD）患者中，该疗法既实现了强有力的靶点结合，也减少了肌肉损伤。基于这一结果，诺华将继续推进del-brax的3期研究。作为诺华通过收购Avidity Biosciences纳入其神经科学管线的三款潜在“first-in-class”疾病修饰AOC疗法之一，del-brax也进一步体现出AOC技术在神经肌肉疾病领域的开发潜力。 此外，多种新型RNA治疗策略也在本季度继续向临床验证迈进。Alltrna宣布AP003获准启动首次人体临床试验，公司称其为首款进入临床阶段的tRNA疗法。礼来（Eli Lilly and Company）公布了VERVE-102的早期临床数据。该疗法通过GalNAc偶联脂质纳米颗粒（LNP）递送编码腺嘌呤碱基编辑器的mRNA和靶向PCSK9的引导RNA（gRNA），旨在通过一次给药实现对肝脏PCSK9基因的持久关闭。新闻稿指出，在最高剂量组中，单次给药后PCSK9最高下降88%，LDL-C最高下降62%；部分受试者随访时间最长达到18个月，仍观察到持久疗效，支持其作为高胆固醇血症一次性治疗方案的潜力。Wave Life Sciences旗下RNA编辑寡核苷酸（AIMer）疗法WVE-006则在α-1抗胰蛋白酶缺乏症（AATD）相关研究中取得积极进展。RestorAATion-2试验数据显示，单次给予WVE-006即可使循环中的突变型Z-AAT较基线出现强效、剂量依赖性下降，降幅最高可达59.1%（600 mg）。该试验结果也推动公司与FDA讨论潜在加速批准路径。 研发合作与融资进展 在产业合作与融资方面，2026年第二季度，多项围绕RNAi管线与平台的合作相继达成。5月，Arrowhead Pharmaceuticals与Madrigal Pharmaceuticals达成全球独家许可协议，后者将获得ARO-PNPLA3的开发、生产和商业化权益。ARO-PNPLA3是一款靶向PNPLA3的临床阶段siRNA疗法，拟用于治疗携带PNPLA3 I148M变异的代谢功能障碍相关脂肪性肝炎（MASH）患者。根据协议，Madrigal将向Arrowhead支付2500万美元首付款，Arrowhead还有资格获得最高9.75亿美元的开发、监管及销售里程碑付款。同月，GSK与时安生物（SiranBio）就SA030达成一项潜在总额最高达10.05亿美元的全球独家许可协议。SA030是一款靶向ALK7的长效siRNA药物，已进入1期临床试验，用于治疗代谢与心血管疾病。 围绕RNAi平台的合作与资本支持也持续升温。Alnylam与Inceptive达成一项潜在总额最高达20亿美元的人工智能（AI）战略合作。双方计划将Alnylam在RNAi领域的研发平台和20余年专有siRNA数据，与Inceptive的基础模型和AI能力相结合，用于加速RNAi疗法发现和寡核苷酸设计。与此同时，City Therapeutics完成9950万美元B轮融资，所得资金将用于推进其RNAi工程平台和管线项目，包括正在开展1期临床试验的CITY-FXI，以及计划于2026年底前进入临床的另外两个项目。 在ASO领域，Ionis与Recordati就zilganersen达成美国以外地区的授权合作。Zilganersen是一款用于治疗亚历山大病（AxD）的在研ASO疗法，其新药申请已获美国FDA受理，并被授予优先审评资格，PDUFA日期为2026年9月22日。 本季度，靶向递送平台开发也取得多项进展。Vivatides Therapeutics完成超额认购的5400万美元A轮融资，所得资金将用于推进其肝外RNA靶向治疗平台和多个管线项目进入临床开发。该公司构建了差异化的肝外递送平台，覆盖siRNA和ASO两类技术路线，并在配体偶联、递送效率、组织靶向特异性及安全性等方面取得重要进展。Interna Therapeutics与第一三共（Daiichi Sankyo）达成研究合作，双方将评估Interna分子纳米马达（Molecular Nano Motor，MNM）技术作为靶向治疗递送增强工具的应用潜力。MNM平台旨在实现多种治疗载荷的高效细胞内递送，包括siRNA、反义寡核苷酸、多肽及其他大分子，且无需依赖传统递送系统。通过增强药物进入细胞的能力和组织穿透性，MNM有望提升多种适应症中靶向治疗的疗效。 这些进展也表明，递送体系正在成为寡核苷酸疗法进一步突破适应症边界的关键环节。无论是siRNA、ASO、mRNA，还是RNA编辑等新型治疗模式，如何将治疗载荷高效、稳定并可规模化地递送至目标组织和细胞，正越来越成为决定项目临床转化和后续产业化的重要因素。因此，在递送技术持续创新的同时，能够支持脂质材料研发、LNP制剂开发、工艺放大和CMC生产的一体化平台能力，也在RNA药物开发中发挥着越来越重要的作用。 在LNP递送体系快速发展的背景下，脂质材料的研发与合成能力正成为寡核苷酸药物研发的重要基础。药明康德旗下合全药业（WuXi STA）的脂质纳米颗粒平台旨在帮助客户项目从研发阶段快速推进到临床和商业化生产阶段。 平台的LNP研发实验室配备了多通道微混合系统、不同规模的切向流过滤（TFF）系统、无菌过滤系统和分析设备。并且配备其它混合技术与设备，例如MIVM、微流体、精密纳米系统和LNP挤出系统。研发实验室可进行LNP可行性研究、制剂开发和工艺开发。 平台的LNP生产车间为模块化设计，将多通道芯片、微混合系统和复杂的制备系统整合到一个以多通道微混合器为核心的LNP生产平台中，在药物载量、脂质体粒径控制和包封效率方面有显著的优势。此外，模块化设计提供了更高的灵活性，使该平台能够支持各种生产规模，每批可达10-50升。 值得一提的是，合全药业也可以提供寡核苷酸和特定功能性脂质（如可电离脂质和聚乙二醇化脂质）的合成和生产服务。该平台提供端到端服务，包含原料药、制剂和分析支持的一体化CMC开发和生产服务。同时，药明康德旗下WuXi TIDES团队全面掌握多种偶联位点与修饰技术，针对siRNA、ASO等不同类型开发出超过20种可供偶联的脂质类型，并在酰胺偶联、点击化学等多种偶联技术上积累了丰富实操经验。 总体来看，2026年第二季度寡核苷酸疗法行业延续了较高活跃度。一方面，脂质代谢疾病、慢性乙肝、神经系统疾病、罕见病和自身免疫疾病等适应症迎来多项监管推进；另一方面，肝外递送和非肝脏适应症拓展成为临床开发的重要趋势，相关探索已延伸至肿瘤免疫、心血管疾病、神经肌肉疾病、RNA编辑和tRNA疗法等更广泛领域。与此同时，抗体偶联寡核苷酸、GalNAc偶联脂质纳米颗粒、RNA编辑寡核苷酸以及分子纳米马达等新型递送和治疗策略，正在不断拓展寡核苷酸疗法的边界。随着更多关键临床研究、监管申请、授权合作和平台融资落地，寡核苷酸疗法正在从相对成熟的肝脏靶向应用，逐步走向更多具有未满足医疗需求的疾病治疗场景。 Q2 2026 Review of Oligonucleotide Drugs Oligonucleotide drugs have become an important focus in global new drug development and have seen rapid application across multiple therapeutic areas in recent years. To help partners advance oligonucleotide drugs from the laboratory to the clinic more efficiently, WuXi AppTec has built an integrated solution around oligonucleotides and related chemically conjugated drugs. The solution covers key areas including custom synthesis, covalent conjugation, process development, and CMC, providing strong support for the discovery and development of oligonucleotides and complex conjugated drugs. This article reviews key developments in the oligonucleotide field in the second quarter of 2026 and highlights the latest dynamics and trends in this rapidly evolving area. Regulatory Progress In the second quarter of 2026, oligonucleotide therapeutics achieved several key regulatory milestones across metabolic diseases, rare diseases, neurological disorders, and chronic hepatitis B. In lipid metabolism disorders, Ionis Pharmaceuticals’ antisense oligonucleotide (ASO) therapy Tryngolza (olezarsen) received approval for an expanded indication from the U.S. FDA in June as an adjunct to diet to reduce triglyceride levels and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG). In the same month, Arrowhead Pharmaceuticals’ siRNA therapy Redemplo (plozasiran) was approved in the European Union to reduce triglyceride levels in adults with familial chylomicronemia syndrome (FCS). Both approved therapies target apolipoprotein C-III (apoC-III), a key regulator of triglyceride metabolism. Neurological disorders and rare diseases also saw regulatory advances. Biogen’s ASO therapy salanersen received Breakthrough Therapy designation from the U.S. FDA for the treatment of spinal muscular atrophy (SMA). According to the company, salanersen is designed to modulate SMN2 pre-mRNA splicing and has the potential to enable once-yearly dosing. Praxis Precision Medicines’ ASO therapy elsunersen also received Breakthrough Therapy designation from the U.S. FDA during the quarter for the treatment of seizures associated with early-onset developmental and epileptic encephalopathy caused by SCN2A gain-of-function variants (SCN2A-DEE). In Duchenne muscular dystrophy (DMD), Dyne Therapeutics submitted a biologics license application (BLA) to the U.S. FDA during the quarter for z-rostudirsen, which is intended for patients with DMD amenable to exon 51 skipping. Z-rostudirsen consists of a phosphorodiamidate morpholino oligomer (PMO) conjugated to an antibody fragment targeting TfR1. As TfR1 is highly expressed in muscle tissue, this design aims to leverage receptor-mediated delivery to enhance PMO entry into relevant tissues and cells, promote exon 51 skipping, and thereby produce near full-length dystrophin. In addition, cemdisiran, a subcutaneously administered siRNA therapy targeting complement C5 and co-developed by Regeneron Pharmaceuticals and Alnylam Pharmaceuticals, also made regulatory progress during the quarter. Regulatory applications for cemdisiran in generalized myasthenia gravis (gMG) have been accepted by the U.S. FDA and the European Medicines Agency (EMA). The U.S. FDA also granted the application Priority Review, with a target action date in November 2026; a European Commission decision is expected in the second half of 2027. In chronic hepatitis B (CHB), the U.S. FDA accepted the new drug application (NDA) for bepirovirsen, a potential first-in-class ASO drug co-developed by Ionis and GSK, and granted it Priority Review. The PDUFA date for the application is set for October 26, 2026. The therapy has also received Breakthrough Therapy designation from the FDA. Meanwhile, Arbutus Biopharma’s RNAi therapy imdusiran received Fast Track designation from the U.S. FDA for the treatment of chronic hepatitis B. Clinical Progress In clinical development, the second quarter of 2026 further highlighted the growing trend of oligonucleotide therapeutics expanding beyond liver-targeted indications. Clinical exploration is now extending into broader areas, including neurological disorders, muscle diseases, cardiovascular diseases, cancer immunotherapy, and RNA editing. In oncology, mRNA cancer vaccines continued to make progress. Early study results for autogene cevumeran, an individualized neoantigen mRNA vaccine jointly developed by BioNTech and Genentech, showed that among eight pancreatic cancer patients who mounted an immune response to the vaccine, seven patients (87.5%) remained alive four to six years after surgery. In the field of scalable off-the-shelf cancer vaccines, Moderna also reported results during the quarter from a Phase 1/2 clinical trial of mRNA-4359 in combination with the anti-PD-1 antibody Keytruda (pembrolizumab) as a first-line therapy for previously untreated locally advanced or metastatic melanoma. Data showed that among 12 evaluable patients, the objective response rate (ORR) reached 83%, including two complete responses (CRs) and eight partial responses (PRs), while the disease control rate (DCR) was 92%. Notably, treatment responses were observed regardless of baseline PD-L1 expression, suggesting that the therapy may have potential applicability across a broad patient population. In cardiovascular-related diseases, Kardigan’s once-monthly angiotensinogen (AGT)-targeting ASO therapy tonlamarsen showed biomarker reduction and a trend toward blood pressure improvement in a Phase 2 study in patients with acute severe hypertension. From baseline to Week 20 after tonlamarsen treatment, patients’ plasma AGT levels decreased significantly, and office systolic blood pressure (oSBP) also showed a clinically meaningful reduction (-6.7 mmHg). HAYA Therapeutics’ pipeline HTX-001 has completed dosing of the first cohort in a Phase 1 clinical trial for the treatment of non-obstructive hypertrophic cardiomyopathy (nHCM). HTX-001 is an ASO therapy targeting the long non-coding RNA (lncRNA) WISPER and is designed to treat cardiac fibrosis by modulating the state of cardiac fibroblasts. Rare diseases and neuromuscular disorders remained among the most active areas for oligonucleotide clinical progress during the quarter. Entrada Therapeutics announced positive first-cohort results from the Phase 1/2 ELEVATE-44-201 study of ENTR-601-44 in patients with DMD. The investigational oligonucleotide therapy is designed to promote exon 44 skipping. According to the company’s press release, the study observed increased exon skipping and dystrophin expression, supporting advancement into subsequent dose cohorts. Novartis announced in June that its investigational antibody oligonucleotide conjugate (AOC) del-brax met the primary endpoint and key secondary endpoints in the biomarker cohort of a Phase 1/2 study. Reductions in KHDC1L (cDUX) and creatine kinase biomarkers indicate that, in patients with facioscapulohumeral muscular dystrophy (FSHD), the therapy achieved strong target engagement and reduced muscle damage. Based on these results, Novartis will continue to advance the Phase 3 study of del-brax. As one of three potential first-in-class disease-modifying AOC therapies added to Novartis’ neuroscience pipeline through its acquisition of Avidity Biosciences, del-brax further demonstrates the development potential of AOC technology in neuromuscular diseases. In addition, multiple novel RNA therapeutic strategies continued to move toward clinical validation during the quarter. Alltrna announced that AP003 was cleared to initiate its first-in-human clinical trial, and the company described it as the first tRNA therapy to enter clinical development. Eli Lilly and Company reported early clinical data for VERVE-102. The therapy uses GalNAc-conjugated lipid nanoparticles (LNPs) to deliver mRNA encoding an adenine base editor and guide RNA (gRNA) targeting PCSK9, with the goal of achieving durable silencing of the hepatic PCSK9 gene through a single administration. According to the company, in the highest-dose group, a single dose led to up to 88% reduction in PCSK9 level and up to 62% reduction in LDL-C. Some participants were followed for up to 18 months, with durable efficacy still observed, supporting its potential as a one-time treatment for hypercholesterolemia. Wave Life Sciences’ RNA editing oligonucleotide therapy WVE-006, an AIMer therapy, also made positive progress in studies related to alpha-1 antitrypsin deficiency (AATD). Data from the RestorAATion-2 trial showed that a single dose of WVE-006 resulted in a potent, dose-dependent reduction from baseline in circulating mutant Z-AAT, with reductions of up to 59.1% at 600 mg. These results also supported the company’s discussions with the FDA regarding a potential accelerated approval pathway. Partnerships and Financing  In industry collaborations and financing, the second quarter of 2026 saw multiple agreements centered on RNAi pipelines and platforms. In May, Arrowhead Pharmaceuticals and Madrigal Pharmaceuticals entered into a global exclusive licensing agreement under which Madrigal will obtain the rights to develop, manufacture, and commercialize ARO-PNPLA3. ARO-PNPLA3 is a clinical-stage siRNA therapy targeting PNPLA3 and is intended for the treatment of patients with metabolic dysfunction-associated steatohepatitis (MASH) who carry the PNPLA3 I148M variant. Under the agreement, Madrigal will pay Arrowhead an upfront payment of $25 million, and Arrowhead is eligible to receive up to $975 million in development, regulatory, and sales milestone payments. In the same month, GSK and SiranBio entered into a global exclusive licensing agreement for SA030, with a potential total value of up to $1.005 billion. SA030 is a long-acting siRNA drug targeting ALK7 and has entered Phase 1 clinical trials for the treatment of metabolic and cardiovascular diseases. Collaboration and capital support around RNAi platforms also continued to gain momentum. Alnylam and Inceptive entered into a strategic artificial intelligence (AI) collaboration with a potential total value of up to $2 billion. The two companies plan to combine Alnylam’s RNAi R&D platform and more than 20 years of proprietary siRNA data with Inceptive’s foundation models and AI capabilities to accelerate RNAi therapeutic discovery and oligonucleotide design. Meanwhile, City Therapeutics completed a $99.5 million Series B financing, with proceeds to be used to advance its RNAi engineering platform and pipeline, including CITY-FXI, which is currently in a Phase 1 clinical trial, as well as two additional programs planned to enter the clinic by the end of 2026. In the ASO field, Ionis and Recordati entered into a licensing collaboration for zilganersen outside the United States. Zilganersen is an investigational ASO therapy for Alexander disease (AxD). Its new drug application has been accepted by the U.S. FDA and granted Priority Review, with a PDUFA date of September 22, 2026. Targeted delivery platform development also made several advances during the quarter. Vivatides Therapeutics completed an oversubscribed $54 million Series A financing, with proceeds to support the advancement of its extrahepatic RNA-targeted therapeutic platform and multiple pipeline programs into clinical development. The company has built a differentiated extrahepatic delivery platform covering both siRNA and ASO technology approaches and has made important progress in ligand conjugation, delivery efficiency, tissue-targeting specificity, and safety. Interna Therapeutics entered into a research collaboration with Daiichi Sankyo, under which the parties will evaluate the potential of Interna’s Molecular Nano Motor (MNM) technology as a delivery-enhancing tool for targeted therapeutic modalities. The MNM platform is designed to enable efficient intracellular delivery of multiple therapeutic payloads, including siRNA, antisense oligonucleotides, peptides, and other macromolecules, without relying on traditional delivery systems. By enhancing drug entry into cells and tissue penetration, MNM has the potential to improve the efficacy of targeted therapies across multiple indications. These developments also indicate that delivery systems are becoming a critical component for oligonucleotide therapeutics to further expand the boundaries of their indications. Whether for siRNA, ASO, mRNA, or emerging modalities such as RNA editing, the ability to deliver therapeutic payloads to target tissues and cells efficiently, stably, and at scale is increasingly becoming a key factor in determining clinical translation and future industrialization. Therefore, as delivery technologies continue to evolve, integrated platform capabilities that support lipid material R&D, LNP formulation development, process scale-up, and CMC production are playing an increasingly important role in RNA drug development. Against the backdrop of rapid development in LNP delivery systems, lipid material R&D and synthesis capabilities are becoming an important foundation for oligonucleotide drug development. WuXi STA, an integral part of WuXi AppTec, has established an integrated lipid nanoparticle (LNP) development and manufacturing platform designed to support RNA therapeutics programs from early development through clinical and commercial production. As LNP and liposomal delivery systems rapidly advance across modalities such as mRNA, siRNA, and other nucleic acid therapeutics, the ability to design, synthesize, and manufacture high-quality lipid materials has become a critical foundation for successful drug development.  WuXi STA’s platform combines advanced formulation expertise with scalable manufacturing infrastructure to help partners efficiently translate innovative RNA medicines into clinical candidates. The dedicated LNP development laboratories are equipped with multi-channel micro-mixing systems, multiple scales of tangential flow filtration (TFF) systems, sterile filtration units, and comprehensive analytical instrumentation. In addition, the laboratories incorporate diverse mixing technologies and equipment, including MIVM systems, microfluidic platforms, precision nano systems, and LNP extrusion systems, enabling feasibility studies, formulation development, and process optimization for a wide range of nucleic acid delivery applications.  To support seamless scale-up, WuXi STA operates a modular LNP manufacturing suite that integrates multi-channel chips, micro-mixing technologies, and complex preparation systems within a production platform centered on multi-channel micro-mixers. This design enables precise control of drug loading, particle size distribution, and encapsulation efficiency while providing the flexibility to accommodate a variety of production scales, with batch volumes typically ranging from 10 to 50 liters.  Importantly, WuXi STA can also synthesize and manufacture oligonucleotides as well as functional lipids, including ionizable lipids and PEGylated lipids, further strengthening its capabilities in nucleic acid delivery systems. Through this end-to-end platform, WuXi STA provides integrated CMC services encompassing API development, formulation development, analytical support, and GMP manufacturing, helping global partners accelerate the development of RNA-based therapeutics from concept to clinic and beyond.  At the same time, the WuXi TIDES team, part of WuXi AppTec, has developed comprehensive expertise in a wide range of conjugation sites and modification technologies. For different modalities such as siRNA and ASO, the team has developed more than 20 types of lipids available for conjugation and has accumulated extensive hands-on experience across multiple conjugation technologies, including amide coupling and click chemistry. Overall, the oligonucleotide therapeutics sector maintained a high level of activity in the second quarter of 2026. On one hand, multiple indications, including lipid metabolism disorders, chronic hepatitis B, neurological disorders, rare diseases, and autoimmune diseases, achieved important regulatory progress. On the other hand, extrahepatic delivery and expansion into non-liver indications have become important trends in clinical development, with exploration extending into broader areas such as cancer immunotherapy, cardiovascular diseases, neuromuscular disorders, RNA editing, and tRNA therapies. At the same time, new delivery and therapeutic strategies, including antibody oligonucleotide conjugates, GalNAc-conjugated lipid nanoparticles, RNA editing oligonucleotides, and Molecular Nano Motor technology, are continuing to expand the boundaries of oligonucleotide therapeutics. As more pivotal clinical studies, regulatory applications, licensing collaborations, and platform financings move forward, oligonucleotide therapeutics are advancing from relatively mature liver-targeted applications toward a broader range of disease areas with significant unmet medical needs. 参考资料： [1] 各家公司新闻稿 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新