突破性慢性乙肝療法有望今年獲批；降血脂！FDA再批準(zhǔn)ASO療法…… | Bilingual

編者按：寡核苷酸藥物已成為全球新藥開發(fā)的重要熱點，近年來在不同疾病多個領(lǐng)域獲得快速應(yīng)用。為幫助合作伙伴更高效地推動寡核苷酸藥物從實驗室走向臨床，藥明康德圍繞寡核苷酸及其相關(guān)化學(xué)偶聯(lián)藥物構(gòu)建了一體化解決方案，覆蓋定制合成、共價連接、工藝開發(fā)以及CMC等關(guān)鍵環(huán)節(jié)，為寡核苷酸及復(fù)雜偶聯(lián)藥物的發(fā)現(xiàn)與開發(fā)提供有力支持。本文將盤點2026年第二季度寡核苷酸領(lǐng)域的重要進(jìn)展，帶您了解這一快速發(fā)展領(lǐng)域的最新動態(tài)與趨勢。

監(jiān)管進(jìn)展

2026年第二季度，寡核苷酸療法在代謝疾病、罕見病、神經(jīng)系統(tǒng)疾病及慢性乙肝等領(lǐng)域迎來多項關(guān)鍵監(jiān)管進(jìn)展。在脂質(zhì)代謝疾病領(lǐng)域，Ionis Pharmaceuticals旗下反義寡核苷酸（ASO）療法Tryngolza（olezarsen）在6月獲得美國FDA擴展適應(yīng)癥批準(zhǔn)，作為飲食控制的輔助療法，用于降低成人重度高甘油三酯血癥（sHTG）患者的甘油三酯水平和急性胰腺炎風(fēng)險。同月，Arrowhead Pharmaceuticals旗下siRNA療法Redemplo（plozasiran）在歐盟獲批，用于降低成人家族性乳糜微粒血癥綜合征（FCS）患者的甘油三酯水平。這兩款獲批療法均靶向甘油三酯代謝的關(guān)鍵調(diào)節(jié)因子載脂蛋白C-III（apoC-III）。

神經(jīng)系統(tǒng)疾病和罕見病方向也迎來監(jiān)管推進(jìn)。渤健（Biogen）旗下ASO療法salanersen獲得美國FDA突破性療法認(rèn)定，用于治療脊髓性肌萎縮癥（SMA）。根據(jù)新聞稿，salanersen旨在調(diào)節(jié)SMN2前體mRNA剪接，有望實現(xiàn)每年一次給藥。Praxis Precision Medicines旗下ASO療法elsunersen也在本季度獲得美國FDA突破性療法認(rèn)定，用于治療由SCN2A功能獲得性變異導(dǎo)致的早發(fā)性發(fā)育性癲癇性腦病（SCN2A-DEE）相關(guān)癲癇發(fā)作。

在杜氏肌營養(yǎng)不良癥（DMD）領(lǐng)域，Dyne Therapeutics本季度向美國FDA提交了z-rostudirsen的生物制品許可申請（BLA），用于治療適合外顯子51跳躍的DMD患者。Z-rostudirsen由磷酰二胺嗎啉寡聚體（PMO）與靶向TfR1的抗體片段偶聯(lián)而成。由于TfR1在肌肉組織中具有較高表達(dá)，這一設(shè)計旨在借助受體介導(dǎo)的遞送機制，提高PMO進(jìn)入相關(guān)組織和細(xì)胞的能力，并促進(jìn)外顯子51跳躍，從而產(chǎn)生近全長抗肌萎縮蛋白。此外，再生元（Regeneron Pharmaceuticals）與Alnylam Pharmaceuticals合作開發(fā)的皮下注射、補體C5靶向siRNA療法cemdisiran也在本季度取得監(jiān)管進(jìn)展。該療法用于治療全身型重癥肌無力（gMG）的監(jiān)管申請已獲美國FDA和歐洲藥品管理局（EMA）受理，美國FDA還授予該申請優(yōu)先審評資格，目標(biāo)審評日期為2026年11月；歐盟委員會預(yù)計將在2027年下半年作出決定。

在慢性乙型肝炎（CHB）領(lǐng)域，美國FDA已受理Ionis與GSK聯(lián)合開發(fā)的潛在“first-in-class”ASO藥物bepirovirsen的新藥申請（NDA），并授予其優(yōu)先審評資格，該申請的PDUFA日期定為2026年10月26日。同時，該療法也獲得FDA突破性療法認(rèn)定。與此同時，Arbutus Biopharma旗下RNAi療法imdusiran獲得美國FDA快速通道資格，用于治療慢性乙肝。

臨床進(jìn)展

在臨床研究方面，2026年第二季度，寡核苷酸療法向肝臟以外適應(yīng)癥拓展的趨勢更加明顯，相關(guān)探索已延伸至神經(jīng)系統(tǒng)疾病、肌肉疾病、心血管疾病、腫瘤免疫，并覆蓋RNA編輯等更廣泛領(lǐng)域。

在腫瘤治療領(lǐng)域，mRNA癌癥疫苗持續(xù)取得隨訪和早期臨床進(jìn)展。BioNTech和基因泰克（Genentech）聯(lián)合開發(fā)的個體化新抗原mRNA疫苗autogene cevumeran的早期研究結(jié)果顯示，在8名對疫苗產(chǎn)生免疫應(yīng)答的胰腺癌患者中，有7名（87.5%）在手術(shù)后4至6年時仍然存活。在可規(guī)模化的“現(xiàn)貨型”（off-the-shelf）癌癥疫苗方面，Moderna在本季度公布了旗下mRNA-4359聯(lián)合抗PD-1抗體Keytruda（pembrolizumab）作為既往未經(jīng)治療的局部晚期或轉(zhuǎn)移性黑色素瘤一線療法的1/2期臨床試驗結(jié)果。數(shù)據(jù)顯示，12例可評估患者的客觀緩解率（ORR）達(dá)到83%，其中包括2例完全緩解（CR）和8例部分緩解（PR），疾病控制率（DCR）為92%。值得關(guān)注的是，無論患者基線PD-L1表達(dá)水平如何，研究中均觀察到治療應(yīng)答，提示該療法可能具有較廣的潛在適用人群。

在心血管相關(guān)疾病方向，Kardigan旗下每月給藥一次的血管緊張素原（AGT）靶向ASO療法tonlamarsen也在急性重度高血壓患者的2期研究中顯示出生物標(biāo)志物降低和血壓改善趨勢。從基線至接受tonlamarsen治療后第20周，患者血漿AGT水平顯著下降，門診收縮壓（oSBP）也出現(xiàn)具有臨床意義的降低（-6.7 mmHg）。HAYA Therapeutics旗下候選療法HTX-001用于治療非阻塞性肥厚型心肌病（nHCM）的1期臨床試驗，已完成首個隊列給藥。HTX-001是一款靶向長鏈非編碼RNA（lncRNA）WISPER的反義寡核苷酸療法，旨在通過調(diào)控心臟成纖維細(xì)胞狀態(tài)來治療心臟纖維化。

罕見病和神經(jīng)肌肉疾病仍是本季度寡核苷酸療法臨床進(jìn)展最密集的領(lǐng)域之一。Entrada Therapeutics公布了ENTR-601-44在DMD患者中的1/2期ELEVATE-44-201研究首個隊列積極結(jié)果。該藥物是一款旨在促進(jìn)外顯子44跳躍的在研寡核苷酸療法。公司新聞稿顯示，研究觀察到外顯子跳躍和抗肌萎縮蛋白表達(dá)增加，支持進(jìn)一步推進(jìn)后續(xù)劑量隊列。諾華（Novartis）則在6月公布，其在研抗體偶聯(lián)寡核苷酸藥物（AOC）del-brax在1/2期研究的生物標(biāo)志物隊列中達(dá)到主要終點和關(guān)鍵次要終點。KHDC1L（cDUX）和肌酸激酶生物標(biāo)志物水平的下降表明，在面肩肱型肌營養(yǎng)不良癥（FSHD）患者中，該療法既實現(xiàn)了強有力的靶點結(jié)合，也減少了肌肉損傷。基于這一結(jié)果，諾華將繼續(xù)推進(jìn)del-brax的3期研究。作為諾華通過收購Avidity Biosciences納入其神經(jīng)科學(xué)管線的三款潛在“first-in-class”疾病修飾AOC療法之一，del-brax也進(jìn)一步體現(xiàn)出AOC技術(shù)在神經(jīng)肌肉疾病領(lǐng)域的開發(fā)潛力。

此外，多種新型RNA治療策略也在本季度繼續(xù)向臨床驗證邁進(jìn)。Alltrna宣布AP003獲準(zhǔn)啟動首次人體臨床試驗，公司稱其為首款進(jìn)入臨床階段的tRNA療法。禮來（Eli Lilly and Company）公布了VERVE-102的早期臨床數(shù)據(jù)。該療法通過GalNAc偶聯(lián)脂質(zhì)納米顆粒（LNP）遞送編碼腺嘌呤堿基編輯器的mRNA和靶向PCSK9的引導(dǎo)RNA（gRNA），旨在通過一次給藥實現(xiàn)對肝臟PCSK9基因的持久關(guān)閉。新聞稿指出，在最高劑量組中，單次給藥后PCSK9最高下降88%，LDL-C最高下降62%；部分受試者隨訪時間最長達(dá)到18個月，仍觀察到持久療效，支持其作為高膽固醇血癥一次性治療方案的潛力。Wave Life Sciences旗下RNA編輯寡核苷酸（AIMer）療法WVE-006則在α-1抗胰蛋白酶缺乏癥（AATD）相關(guān)研究中取得積極進(jìn)展。RestorAATion-2試驗數(shù)據(jù)顯示，單次給予WVE-006即可使循環(huán)中的突變型Z-AAT較基線出現(xiàn)強效、劑量依賴性下降，降幅最高可達(dá)59.1%（600 mg）。該試驗結(jié)果也推動公司與FDA討論潛在加速批準(zhǔn)路徑。

研發(fā)合作與融資進(jìn)展

在產(chǎn)業(yè)合作與融資方面，2026年第二季度，多項圍繞RNAi管線與平臺的合作相繼達(dá)成。5月，Arrowhead Pharmaceuticals與Madrigal Pharmaceuticals達(dá)成全球獨家許可協(xié)議，后者將獲得ARO-PNPLA3的開發(fā)、生產(chǎn)和商業(yè)化權(quán)益。ARO-PNPLA3是一款靶向PNPLA3的臨床階段siRNA療法，擬用于治療攜帶PNPLA3 I148M變異的代謝功能障礙相關(guān)脂肪性肝炎（MASH）患者。根據(jù)協(xié)議，Madrigal將向Arrowhead支付2500萬美元首付款，Arrowhead還有資格獲得最高9.75億美元的開發(fā)、監(jiān)管及銷售里程碑付款。同月，GSK與時安生物（SiranBio）就SA030達(dá)成一項潛在總額最高達(dá)10.05億美元的全球獨家許可協(xié)議。SA030是一款靶向ALK7的長效siRNA藥物，已進(jìn)入1期臨床試驗，用于治療代謝與心血管疾病。

圍繞RNAi平臺的合作與資本支持也持續(xù)升溫。Alnylam與Inceptive達(dá)成一項潛在總額最高達(dá)20億美元的人工智能（AI）戰(zhàn)略合作。雙方計劃將Alnylam在RNAi領(lǐng)域的研發(fā)平臺和20余年專有siRNA數(shù)據(jù)，與Inceptive的基礎(chǔ)模型和AI能力相結(jié)合，用于加速RNAi療法發(fā)現(xiàn)和寡核苷酸設(shè)計。與此同時，City Therapeutics完成9950萬美元B輪融資，所得資金將用于推進(jìn)其RNAi工程平臺和管線項目，包括正在開展1期臨床試驗的CITY-FXI，以及計劃于2026年底前進(jìn)入臨床的另外兩個項目。

在ASO領(lǐng)域，Ionis與Recordati就zilganersen達(dá)成美國以外地區(qū)的授權(quán)合作。Zilganersen是一款用于治療亞歷山大病（AxD）的在研ASO療法，其新藥申請已獲美國FDA受理，并被授予優(yōu)先審評資格，PDUFA日期為2026年9月22日。

本季度，靶向遞送平臺開發(fā)也取得多項進(jìn)展。Vivatides Therapeutics完成超額認(rèn)購的5400萬美元A輪融資，所得資金將用于推進(jìn)其肝外RNA靶向治療平臺和多個管線項目進(jìn)入臨床開發(fā)。該公司構(gòu)建了差異化的肝外遞送平臺，覆蓋siRNA和ASO兩類技術(shù)路線，并在配體偶聯(lián)、遞送效率、組織靶向特異性及安全性等方面取得重要進(jìn)展。Interna Therapeutics與第一三共（Daiichi Sankyo）達(dá)成研究合作，雙方將評估Interna分子納米馬達(dá)（Molecular Nano Motor，MNM）技術(shù)作為靶向治療遞送增強工具的應(yīng)用潛力。MNM平臺旨在實現(xiàn)多種治療載荷的高效細(xì)胞內(nèi)遞送，包括siRNA、反義寡核苷酸、多肽及其他大分子，且無需依賴傳統(tǒng)遞送系統(tǒng)。通過增強藥物進(jìn)入細(xì)胞的能力和組織穿透性，MNM有望提升多種適應(yīng)癥中靶向治療的療效。

這些進(jìn)展也表明，遞送體系正在成為寡核苷酸療法進(jìn)一步突破適應(yīng)癥邊界的關(guān)鍵環(huán)節(jié)。無論是siRNA、ASO、mRNA，還是RNA編輯等新型治療模式，如何將治療載荷高效、穩(wěn)定并可規(guī)模化地遞送至目標(biāo)組織和細(xì)胞，正越來越成為決定項目臨床轉(zhuǎn)化和后續(xù)產(chǎn)業(yè)化的重要因素。因此，在遞送技術(shù)持續(xù)創(chuàng)新的同時，能夠支持脂質(zhì)材料研發(fā)、LNP制劑開發(fā)、工藝放大和CMC生產(chǎn)的一體化平臺能力，也在RNA藥物開發(fā)中發(fā)揮著越來越重要的作用。

在LNP遞送體系快速發(fā)展的背景下，脂質(zhì)材料的研發(fā)與合成能力正成為寡核苷酸藥物研發(fā)的重要基礎(chǔ)。藥明康德旗下合全藥業(yè)（WuXi STA）的脂質(zhì)納米顆粒平臺旨在幫助客戶項目從研發(fā)階段快速推進(jìn)到臨床和商業(yè)化生產(chǎn)階段。

平臺的LNP研發(fā)實驗室配備了多通道微混合系統(tǒng)、不同規(guī)模的切向流過濾（TFF）系統(tǒng)、無菌過濾系統(tǒng)和分析設(shè)備。并且配備其它混合技術(shù)與設(shè)備，例如MIVM、微流體、精密納米系統(tǒng)和LNP擠出系統(tǒng)。研發(fā)實驗室可進(jìn)行LNP可行性研究、制劑開發(fā)和工藝開發(fā)。

平臺的LNP生產(chǎn)車間為模塊化設(shè)計，將多通道芯片、微混合系統(tǒng)和復(fù)雜的制備系統(tǒng)整合到一個以多通道微混合器為核心的LNP生產(chǎn)平臺中，在藥物載量、脂質(zhì)體粒徑控制和包封效率方面有顯著的優(yōu)勢。此外，模塊化設(shè)計提供了更高的靈活性，使該平臺能夠支持各種生產(chǎn)規(guī)模，每批可達(dá)10-50升。

值得一提的是，合全藥業(yè)也可以提供寡核苷酸和特定功能性脂質(zhì)（如可電離脂質(zhì)和聚乙二醇化脂質(zhì)）的合成和生產(chǎn)服務(wù)。該平臺提供端到端服務(wù)，包含原料藥、制劑和分析支持的一體化CMC開發(fā)和生產(chǎn)服務(wù)。同時，藥明康德旗下WuXi TIDES團(tuán)隊全面掌握多種偶聯(lián)位點與修飾技術(shù)，針對siRNA、ASO等不同類型開發(fā)出超過20種可供偶聯(lián)的脂質(zhì)類型，并在酰胺偶聯(lián)、點擊化學(xué)等多種偶聯(lián)技術(shù)上積累了豐富實操經(jīng)驗。

總體來看，2026年第二季度寡核苷酸療法行業(yè)延續(xù)了較高活躍度。一方面，脂質(zhì)代謝疾病、慢性乙肝、神經(jīng)系統(tǒng)疾病、罕見病和自身免疫疾病等適應(yīng)癥迎來多項監(jiān)管推進(jìn)；另一方面，肝外遞送和非肝臟適應(yīng)癥拓展成為臨床開發(fā)的重要趨勢，相關(guān)探索已延伸至腫瘤免疫、心血管疾病、神經(jīng)肌肉疾病、RNA編輯和tRNA療法等更廣泛領(lǐng)域。與此同時，抗體偶聯(lián)寡核苷酸、GalNAc偶聯(lián)脂質(zhì)納米顆粒、RNA編輯寡核苷酸以及分子納米馬達(dá)等新型遞送和治療策略，正在不斷拓展寡核苷酸療法的邊界。隨著更多關(guān)鍵臨床研究、監(jiān)管申請、授權(quán)合作和平臺融資落地，寡核苷酸療法正在從相對成熟的肝臟靶向應(yīng)用，逐步走向更多具有未滿足醫(yī)療需求的疾病治療場景。

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 Juneas 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, andthe 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.

參考資料：

[1] 各家公司新聞稿

免責(zé)聲明：本文僅作信息交流之目的，文中觀點不代表藥明康德立場，亦不代表藥明康德支持或反對文中觀點。本文也不是治療方案推薦。如需獲得治療方案指導(dǎo)，請前往正規(guī)醫(yī)院就診。

版權(quán)說明：歡迎個人轉(zhuǎn)發(fā)至朋友圈，謝絕媒體或機構(gòu)未經(jīng)授權(quán)以任何形式轉(zhuǎn)載至其他平臺。轉(zhuǎn)載授權(quán)請在「藥明康德」微信公眾號回復(fù)“轉(zhuǎn)載”，獲取轉(zhuǎn)載須知。