编者按：2026年第三季度，寡核苷酸及相关RNA疗法在慢性乙肝、神经系统罕见病、心血管疾病和肿瘤等领域取得多项进展。ASO项目获得新的上市批准，RNAi疗法在双靶点设计与肥胖联合治疗方面持续探索，个体化mRNA疗法及体内碱基编辑也公布了新的临床结果。
随着相关研究不断推进，如何更高效地将科学成果转化为可行的治疗方案，成为推动这一领域发展的重要课题。为帮助合作伙伴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。本文依据官方新闻稿，梳理本季度的监管、临床及产业动态，带您了解这一快速发展领域的最新进展与趋势。
监管进展
慢性乙肝与神经系统罕见病迎来新的上市批准
慢性乙肝领域，GSK宣布，反义寡核苷酸（ASO）疗法Hibsago（bepirovirsen）在日本获批，适用对象为既往接受至少6个月核苷（酸）类似物治疗、开始使用本药时乙肝表面抗原（HBsAg）≤3000 IU/mL且HBV DNA＜90 IU/mL的成人患者。Hibsago通过靶向乙型肝炎病毒RNA，降低病毒RNA及相关蛋白水平，从而有望使患者自身免疫系统重新获得对病毒的控制能力。新闻稿指出，这是Hibsago的全球首次获批，也是日本首个获批用于实现慢性乙肝功能性治愈的治疗方案。
支持批准的B-Well两项3期研究合并数据显示，在基线HBsAg≤3000 IU/mL人群中，接受6个月Hibsago治疗后的功能性治愈应答率约为19％，即1220人中233人达到相应标准，安慰剂组614人中无人达到。在基线HBsAg≤1000 IU/mL亚组中，应答率为26％。新闻稿将功能性治愈定义为停止全部治疗后，HBV DNA和HBsAg持续至少24周检测不到，体现了该项目围绕停药后持续应答开展的治疗探索。
神经系统罕见病方向，Ionis Pharmaceuticals旗下Zanvastro（zilganersen）获美国FDA批准，用于儿童及成人亚历山大病患者。该ASO疗法通过降低胶质纤维酸性蛋白（GFAP）的产生，针对疾病相关机制发挥作用，采用50 mg鞘内给药方案，每季度一次。支持批准的随机、双盲、对照研究结果显示，在预设主要疗效分析人群中，第61周步速较基线变化百分比的调整后最小二乘均值组间差为33.3个百分点，具有统计学显著差异。FDA新闻稿指出，Zanvastro是首款获FDA批准用于治疗亚历山大病的药物，也是首款直接靶向驱动该疾病的异常蛋白积聚的疗法。
偶联寡核苷酸与组合siRNA推进注册开发
在杜氏肌营养不良症（DMD）领域，Dyne Therapeutics的z-rostudirsen（DYNE-251）生物制品许可申请（BLA）获FDA受理，并获得优先审评资格，目标审评日期为2027年1月21日。该候选疗法由靶向转铁蛋白受体1（TfR1）的抗体片段与磷酰二胺吗啉寡聚体（PMO）偶联，拟用于适合外显子51跳跃治疗的DMD患者。此次申请以抗肌萎缩蛋白表达水平作为替代终点寻求加速批准，体现了肌肉递送与外显子跳跃策略在注册开发中的推进。
肿瘤方向，Sirnaomics收到FDA对STP705优化2b期研究设计的积极书面反馈。STP705由靶向TGF-β1的pixofisiran与靶向COX-2的lixadesiran按1：1的比例组成，拟用于原位鳞状细胞癌。拟议研究采用四组随机、双盲、安慰剂对照设计，并行评估组合疗法及两种单药，以明确各组分对治疗效果的贡献。公司表示，该研究将为后续确认性3期研究设计讨论提供依据。
临床进展
肿瘤治疗：个体化mRNA疗法公布3期结果
默沙东与Moderna宣布，个体化新抗原mRNA疗法intismeran autogene联合PD-1抑制剂Keytruda（pembrolizumab），在INTerpath-001研究中达到无复发生存期（RFS）主要终点及无远处转移生存期（DMFS）关键次要终点。研究面向完全切除的IIB至IV期黑色素瘤患者，在预设中期分析中，联合方案相较Keytruda单药显示出具有统计学显著性和临床意义的改善。
Intismeran autogene根据患者肿瘤的独特突变特征设计，旨在诱导针对肿瘤新抗原的免疫应答。此次新闻稿尚未披露具体风险比、置信区间及本次分析的详细疗效数据，研究还将继续评估总生存期等终点。该结果为个体化mRNA疗法在术后辅助治疗中的应用提供了新的后期临床证据。根据新闻稿，这是个体化新抗原疗法以及基于mRNA的癌症疗法首次取得积极的3期临床试验结果，也是首个在黑色素瘤术后辅助治疗中，相较标准治疗Keytruda单药显示出具有临床意义改善的3期研究。
心血管与脂质代谢：临床事件证据与双靶点设计并行
Arrowhead Pharmaceuticals公布靶向APOC3的siRNA疗法plozasiran在SHASTA-3和SHASTA-4中的详细3期结果。两项随机、双盲、安慰剂对照研究共纳入757名重度高甘油三酯血症成人患者，治疗方案为每3个月皮下注射25 mg。第12个月，治疗组甘油三酯较基线的中位降幅分别为79％和81％；甘油三酯降至500 mg/dL以下的患者比例分别为91％和93％，对应安慰剂组为51％和50％。
在预设的两项研究合并分析中，plozasiran相较安慰剂使全部急性胰腺炎事件发生率降低78％，发生率比（RR）为0.22（95％ CI：0.07-0.67）。与单纯观察血脂变化相比，这一结果进一步补充了临床事件层面的证据，为评估APOC3靶向治疗在重度高甘油三酯血症中的作用提供了依据。
该公司还公布了ARO-DIMER-PA的1/2a期单次给药中期顶线数据。该候选疗法通过一个RNAi分子同时靶向PCSK9与APOC3，拟用于混合型高脂血症相关动脉粥样硬化性心血管疾病。新闻稿报告，PCSK9与APOC3的平均最大降幅分别为72％和88％，低密度脂蛋白胆固醇、甘油三酯、非高密度脂蛋白胆固醇和载脂蛋白B的平均最大降幅分别为54%、73%、61%和50%。这些结果为双靶点单分子设计提供了早期人体药效证据。
Alnylam Pharmaceuticals则围绕TTR靶向siRNA疗法vutrisiran，公布了HELIOS-B按基线tafamidis使用情况划分的预设亚组分析。654名随机并接受治疗的ATTR心肌病患者中，259人基线使用tafamidis。在33至36个月，全因死亡及反复心血管事件复合终点的治疗效应方向在不同背景治疗人群中保持一致，该分析为进一步探索TTR沉默策略提供了参考。
罕见病与神经肌肉疾病：关注持续作用和功能结果
Argo Biopharma公布靶向血浆前激肽释放酶（PKK）的siRNA疗法BW-20805治疗遗传性血管性水肿的更新2期结果。截至6月数据截止日，开放标签研究共25人接受给药，主要终点分析包含24人。600 mg每24周给药一次、300 mg每24周给药一次及300 mg每12周给药一次的三组患者。在第29至169天期间，三组患者经时间标准化的月发作率较基线分别下降83％、96％和93％；同期无发作比例分别为50％、75％和62.5％。这些结果支持继续评估较长给药间隔。
在1型强直性肌营养不良症（DM1）领域，Dyne公布抗体片段偶联ASO疗法z-basivarsen（DYNE-101）的ACHIEVE更新结果。该项目靶向毒性DMPK RNA，旨在改善相关剪接异常。分析显示，第6个月，DYNE-101组患者通过视频评估的手部张开时间较基线平均缩短3.2秒，安慰剂组则平均延长0.4秒；第12个月，五次坐站测试时间较基线缩短1.2秒，10米步行/跑步时间缩短0.3秒。
α1抗胰蛋白酶缺乏症方向，Beam Therapeutics公布体内DNA碱基编辑项目BEAM-302的更新1/2期数据。该项目采用脂质纳米颗粒递送编辑组分，旨在纠正疾病相关PiZ变异。截至6月24日，单次给药疗效分析纳入29名可评估患者，最长随访18个月。在60 mg组中，Part A与Part B的总AAT平均稳态浓度分别为14.4 μM和13.5 μM，并观察到突变型Z-AAT下降。公司还披露，全球关键扩展队列已于7月完成首例给药。这些开放标签结果为编辑后蛋白表达的持续性提供了证据，后续仍需观察肺部及肝脏临床结局。
肥胖与凝血：RNAi探索新的治疗场景
肥胖领域，Wave Life Sciences宣布启动WVE-007联合tirzepatide的2a期研究。WVE-007为靶向INHBE的GalNAc-siRNA；研究评估240 mg及400 mg剂量与每周给药一次的tirzepatide联合使用，纳入身体质量指数（BMI）为35至50 kg/m²且合并2型糖尿病的肥胖患者。该研究将进一步探索RNAi与既有肥胖疗法联用的作用，本次公告未披露新的联合治疗人体结果。
同样靶向INHBE的Sirius Therapeutics候选疗法SRSD384，在澳大利亚1/2a期首次人体研究中完成首例给药。该GalNAc偶联siRNA项目的Part A评估单药单次递增剂量，Part B探索与tirzepatide联合使用。WVE-007与SRSD384的推进，呈现了不同开发方围绕INHBE开展单药和联合治疗研究的路径。
凝血方向，Argo的凝血因子XI（FXI）靶向siRNA疗法BW-41012，在澳大利亚1期研究中完成首例给药，并于本季度获得中国国家药品监督管理局临床试验许可。研究在健康志愿者中采用随机、双盲、安慰剂对照及单次递增剂量设计，评估药代动力学、药效学及FXI活性和抗原水平等指标，为其在血栓栓塞性疾病预防方向的后续开发提供依据。
感染预防：双抗原mRNA流感疫苗推进后期研究
GSK公布同时针对血凝素（HA）和神经氨酸酶（NA）的多价mRNA流感疫苗2期结果。Flu-028为随机、观察者盲法研究，共纳入971名成人，评估免疫应答至接种后第181天。公司表示，优化候选疫苗FLUm3HA.b-3NA在年轻及老年成人中，相较对应的已上市标准剂量及高剂量疫苗产生更高免疫应答，并计划于9月启动3期效力研究。该项目也于7月获得FDA快速通道资格。其双抗原设计为季节性流感预防提供了新的研究方向，实际保护效力将由后续研究进一步评估。
研发合作与融资进展
平台合作方面，Wave与GSK的既有研究合作进入候选选择阶段。GSK选定一项采用Wave SpiNA设计的GalNAc-siRNA肝病候选项目，并将其转入自身开发管线，具体靶点及适应症未披露。此次候选选择触发1200万美元里程碑付款。此外，Wave有资格就每个合作项目获得最高3.30亿至3.75亿美元的开发、上市及商业里程碑付款，以及分级销售提成。该事件体现了平台研究合作向具体候选开发的推进。此外，Dyne完成扩大规模的普通股公开发行，募集资金总额约为4.314亿美元，所募资金将用于支持其DMD与DM1项目的注册申报和临床开发，也展现了神经肌肉疾病偶联疗法向临床应用推进的研发进展。
药明康德生物分析部多平台支持寡核苷酸药物生物分析
与传统小分子和生物大分子相比，寡核苷酸药物通常存在高亲水性、多电荷、易发生非特异性相互作用、易受内源性核酸干扰、降解与代谢过程复杂，且临床生物分析需精准区分相似代谢产物、在多个维度之间平衡分析方法的性能，同时还要额外评估核酸骨架、修饰与递送系统等带来的免疫相关风险。针对这些挑战，药明康德生物分析部（BAS）已建立面向寡核苷酸药物的多平台生物分析能力，覆盖药代动力学、免疫原性，以及药效/生物标志物分析。在药代动力学表征方面，BAS可根据寡核苷酸长度、修饰类型、分析对象、样本基质，以及是否需要区分代谢物，选择LC-MS/MS、LC-HRMS/LC-TOF-MS、LC-FLD、Hybrid ELISA/MSD、qPCR、RT-qPCR和ddPCR等方法。LC-MS/MS相关方法可提供较强的结构选择性，支持母体药物和代谢物分析，杂交和PCR相关方法则可为低丰度分析对象或序列特异性检测提供高灵敏度方案。除药代动力学外，BAS还可基于分层策略支持免疫原性评估，并结合RT-qPCR/ddPCR、酶联免疫分析、多因子检测和高灵敏度蛋白检测等平台，支持把基因表达调控、下游蛋白变化及相关生物标志物的综合评估。
总结与展望
本季度产业进展显示，寡核苷酸及相关RNA疗法在特定疾病中的开发正沿不同路径推进：ASO取得新的上市批准，肌肉递送项目进入注册审评，RNAi探索双靶点及肥胖联合治疗，mRNA和体内碱基编辑也提供了新的临床证据。后续值得关注的重点包括关键研究完整结果、较长给药间隔的持续作用，以及联合策略和新型分子设计能否进一步转化为临床获益。
Q3 2026 Review: Oligonucleotide and Related RNA Therapies
In the third quarter of 2026, oligonucleotide and related RNA therapies made progress across chronic hepatitis B, rare neurological diseases, cardiovascular diseases, and oncology. Antisense oligonucleotide (ASO) programs received new marketing approvals, while RNA interference (RNAi) therapies continued to explore dual-target designs and combination treatments for obesity. Personalized mRNA therapies and in vivo base editing also reported new clinical results.
As research advances, translating scientific findings into viable treatment options more efficiently has become an important priority for the field. To help partners advance oligonucleotide drugs from the laboratory to the clinic, WuXi AppTec has established integrated solutions for oligonucleotides and related chemically conjugated drugs. These solutions cover key areas including custom synthesis, covalent conjugation, process development, and chemistry, manufacturing, and controls (CMC), supporting the discovery and development of oligonucleotides and complex conjugated drugs. Drawing on official press releases, this article reviews the quarter’s regulatory developments, clinical results, and industry activity to highlight the latest progress and trends in this rapidly evolving field.
Regulatory Developments
New Marketing Approvals for Chronic Hepatitis B and Rare Neurological Diseases
In chronic hepatitis B, GSK announced that its ASO therapy Hibsago (bepirovirsen) received approval in Japan, marking the drug’s first approval worldwide. The treatment is indicated for adults who have received nucleos(t)ide analogue therapy for at least 6 months and have hepatitis B surface antigen (HBsAg) levels ≤3,000 IU/mL and HBV DNA levels <90 IU/mL when initiating treatment. Hibsago targets hepatitis B virus RNA, reducing viral RNA and protein levels, potentially enabling patients’ own immune systems to regain control of the virus.According to the company, Hibsago is the first treatment approved in Japan to achieve a functional cure for chronic hepatitis B (CHB).
Pooled data from the two Phase 3 B-Well studies supporting the approval showed a functional cure response rate of approximately 19% following 6 months of Hibsago treatment among participants with baseline HBsAg levels ≤3,000 IU/mL. Specifically, 233 of 1,220 participants met the relevant criteria, compared with none of the 614 participants in the placebo group. In the subgroup with baseline HBsAg levels ≤1,000 IU/mL, the response rate was 26%.The press release described functional cure as maintaining the specified virological control criteria for at least 24 weeks after discontinuing all treatment, reflecting the program’s focus on sustained responses after treatment cessation.
In rare neurological diseases, Ionis Pharmaceuticals’ Zanvastro (zilganersen) received U.S. FDA approval for children and adults with Alexander disease. This ASO therapy addresses the disease mechanism by reducing the production of glial fibrillary acidic protein (GFAP). It is administered intrathecally at a dose of 50 mg once every quarter. In the prespecified primary efficacy analysis population, the 50 mg group met the primary endpoint of change in gait speed assessed by the 10-meter walk test at Week 61, with a least-squares mean difference of 33.3% versus the control group.According to the FDA press release, Zanvastro is the first FDA-approved drug for Alexander disease and the first therapy to directly target the abnormal protein accumulation that drives the disease.
Conjugated Oligonucleotides and Combination siRNA Advance Toward Registration
In Duchenne muscular dystrophy (DMD), the FDA accepted Dyne Therapeutics’ biologics license application (BLA) for z-rostudirsen (DYNE-251) and granted Priority Review, with a target review date of January 21, 2027. The investigational therapy consists of an antibody fragment targeting transferrin receptor 1 (TfR1) conjugated to a phosphorodiamidate morpholino oligomer (PMO). It is intended for patients with DMD amenable to exon 51 skipping. The application seeks accelerated approval using dystrophin as a surrogate endpoint, reflecting the progress of muscle delivery and exon-skipping strategies toward registration.
In oncology, Sirnaomics received positive written feedback from the FDA on the optimized design of its Phase 2b study of STP705.STP705 comprises pixofisiran, which targets TGF-β1, and lixadesiran, which targets COX-2, in a 1:1 ratio and is being developed for squamous cell carcinoma in situ. The proposed study uses a four-arm, randomized, double-blind, placebo-controlled design to evaluate the combination and the two monotherapies in parallel, clarifying each component’s contribution to the treatment effect. The company stated that the study would inform subsequent discussions on the design of a confirmatory Phase 3 study.
Clinical Developments
Cancer Treatment: Personalized mRNA Therapy Reports Phase 3 Results
MSD and Moderna announced that the personalized neoantigen mRNA therapy intismeran autogene, combined with the PD-1 inhibitor Keytruda (pembrolizumab), met the primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS) in the INTerpath-001 study. The study enrolled patients with completely resected stage IIB–IV melanoma. At the prespecified interim analysis, the combination demonstrated statistically significant and clinically meaningful improvements compared with Keytruda alone.
Intismeran autogene is designed based on the unique mutational profile of each patient’s tumor to induce immune responses against tumor neoantigens. The press release did not disclose the specific hazard ratios, confidence intervals, or detailed efficacy data from this analysis. The study will continue to assess overall survival and other endpoints. These results provide new late-stage clinical evidence for the use of personalized mRNA therapy in the adjuvant setting following surgery.According to the companies, these are the first positive Phase 3 clinical trial results for both a personalized neoantigen therapy and an mRNA-based cancer therapy. It is also the first Phase 3 study to demonstrate a clinically meaningful improvement over the standard treatment, Keytruda alone, in the adjuvant treatment of resected melanoma.
Cardiovascular Disease and Lipid Metabolism: Clinical Event Evidence and Dual-Target Designs Advance in Parallel
Arrowhead Pharmaceuticals reported detailed Phase 3 results from SHASTA-3 and SHASTA-4 for plozasiran, an siRNA therapy targeting APOC3. The two randomized, double-blind, placebo-controlled studies enrolled a total of 757 adults with severe hypertriglyceridemia. The treatment regimen consisted of a 25 mg subcutaneous injection every 3 months.At Month 12, the median reductions in triglycerides from baseline in the treatment groups were 79% and 81%, respectively. The proportions of patients whose triglyceride levels fell below 500 mg/dL were 91% and 93%, compared with 51% and 50% in the corresponding placebo groups.
In a prespecified pooled analysis of the two studies, plozasiran reduced the incidence of all acute pancreatitis events by 78% compared with placebo, with a relative risk of 0.22 (95% CI: 0.07–0.67). Beyond changes in lipid levels, these findings add evidence on clinical events, supporting the evaluation of APOC3-targeted treatment in severe hypertriglyceridemia.
The company also reported interim topline single-dose data from the Phase 1/2a study of ARO-DIMER-PA. This investigational therapy uses a single RNAi molecule to target both PCSK9 and APOC3 and is being developed for atherosclerotic cardiovascular disease associated with mixed hyperlipidemia. According to the press release, the mean maximum reductions in PCSK9 and APOC3 were 72% and 88%, respectively.The mean maximum reductions in low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein cholesterol, and apolipoprotein B were 54%, 73%, 61%, and 50%, respectively.These results provide early evidence of pharmacodynamic activity in humans for a single-molecule, dual-target design.
Alnylam Pharmaceuticals reported a prespecified subgroup analysis of HELIOS-B for its TTR-targeting siRNA therapy vutrisiran, stratified by baseline tafamidis use. Of the 654 patients with ATTR cardiomyopathy who were randomized and treated, 259 were receiving tafamidis at baseline. Over 33–36 months, the direction of the treatment effect on the composite endpoint of all-cause mortality and recurrent cardiovascular events was consistent across groups with different background treatments. The analysis provides a basis for further exploration of TTR-silencing strategies.
Rare Diseases and Neuromuscular Disorders: Focus on Durability and Functional Outcomes
Argo Biopharma reported updated Phase 2 results for BW-20805, an siRNA therapy targeting plasma prekallikrein (PKK), in hereditary angioedema. As of the June data cutoff, 25 participants had received treatment in the open-label study, with 24 included in the primary endpoint analysis. In the 600 mg every 24 weeks, 300 mg every 24 weeks, and 300 mg every 12 weeks groups,the time-normalized monthly attack rates from Days 29 to 169 decreased from baseline by 83%, 96%, and 93%, respectively. The proportions of participants who remained attack-free during the same period were 50%, 75%, and 62.5%, respectively. These results support further evaluation of longer dosing intervals.
In myotonic dystrophy type 1 (DM1), Dyne reported updated ACHIEVE results for z-basivarsen (DYNE-101), an antibody fragment-conjugated ASO therapy. The program targets toxic DMPK RNA and aims to improve the associated splicing abnormalities. At Month 6, video-assessed hand-opening time decreased from baseline by a mean of 3.2 seconds in the treatment group, whereas the placebo group experienced a mean increase of 0.4 seconds. At Month 12, the time required to complete the five-times sit-to-stand test decreased from baseline by 1.2 seconds, and the 10-meter walk/run time decreased by 0.3 seconds.
In alpha-1 antitrypsin deficiency, Beam Therapeutics reported updated Phase 1/2 data for BEAM-302, an in vivo DNA base-editing program. The program uses lipid nanoparticles to deliver editing components and is designed to correct the disease-associated PiZ variant. As of June 24, the single-dose efficacy analysis included 29 evaluable patients, with follow-up extending to 18 months. In the 60 mg group, the mean steady-state concentrations of total AAT were 14.4 μM in Part A and 13.5 μM in Part B, with reductions in mutant Z-AAT also observed. The company additionally disclosed that the first participant in the global pivotal expansion cohort had been dosed in July. These open-label results provide evidence of sustained protein expression following editing, while pulmonary and hepatic clinical outcomes remain to be assessed.
Obesity and Coagulation: RNAi Explores New Treatment Settings
In obesity, Wave Life Sciences announced the initiation of a Phase 2a study of WVE-007 in combination with tirzepatide. WVE-007 is a GalNAc-siRNA targeting INHBE. The study evaluates doses of 240 mg and 400 mg in combination with weekly tirzepatide in patients with obesity who have a BMI of 35–50 kg/m² and type 2 diabetes. The study will further explore the effects of combining RNAi with an established obesity therapy. The announcement did not disclose new human results for the combination.
Sirius Therapeutics’ SRSD384, another investigational therapy targeting INHBE, achieved first participant dosing in an Australian Phase 1/2a first-in-human study. Part A of the study evaluates single ascending doses of the GalNAc-conjugated siRNA as monotherapy, while Part B explores its use in combination with tirzepatide. The advancement of WVE-007 and SRSD384 illustrates the approaches different developers are taking to evaluate INHBE-targeted therapies as monotherapies and in combination regimens.
In coagulation, Argo’s factor XI (FXI)-targeting siRNA therapy BW-41012 achieved first participant dosing in an Australian Phase 1 study and received clinical trial authorization from China’s National Medical Products Administration during the quarter. The study uses a randomized, double-blind, placebo-controlled, single ascending dose design in healthy volunteers to assess pharmacokinetics, pharmacodynamics, FXI activity and antigen levels, and other measures. These assessments will inform subsequent development for the prevention of thromboembolic diseases.
Infection Prevention: Dual-Antigen mRNA Influenza Vaccine Advances Toward Late-Stage Studies
GSK reported Phase 2 results for a multivalent mRNA influenza vaccine targeting both hemagglutinin (HA) and neuraminidase (NA). Flu-028 was a randomized, observer-blind study that enrolled 971 adults and assessed immune responses through Day 181 after vaccination. The company stated that the optimized vaccine candidate, FLUm3HA.b-3NA, generated higher immune responses in younger and older adults compared with the corresponding licensed standard-dose and high-dose vaccines, and that it planned to initiate a Phase 3 efficacy study in September. The program also received FDA Fast Track designation in July. Its dual-antigen design offers a new research direction for seasonal influenza prevention, with protective efficacy to be further evaluated in subsequent studies.
R&D Collaborations and Financing Developments
In platform collaborations, Wave and GSK’s existing research collaboration entered the candidate-selection stage. GSK selected a GalNAc-siRNA liver disease candidate using Wave’s SpiNA design and moved it into its own development pipeline. The specific target and indication were not disclosed. The candidate selection triggered a $12 million milestone payment. In addition, Wave is eligible to receive up to $330 million–$375 million in development, launch, and commercial milestone payments for each collaboration program, as well as tiered royalties on sales. This development reflects the progression of a platform research collaboration into the development of a specific candidate. Separately, Dyne completed an upsized public offering of common stock, raising approximately $431.4 million in gross proceeds to support regulatory submissions and clinical development for its DMD and DM1 programs. This also reflects the development progress of conjugated therapies for neuromuscular diseases toward clinical use.
WuXi AppTec BAS: Supporting Oligonucleotide Bioanalysis Across Multiple Platforms
Compared with traditional small molecules and biologics, oligonucleotide drugs present challenges including high hydrophilicity, multiple charges, susceptibility to nonspecific interactions, interference from endogenous nucleic acids, and complex degradation and metabolism. Clinical bioanalysis must accurately distinguish closely related metabolites and balance multiple aspects of assay performance. It must also assess additional immune-related risks associated with nucleic acid backbones, modifications, and delivery systems. To address these challenges, WuXi AppTec’s Bioanalytical Services (BAS) department has established bioanalytical capabilities across multiple platforms for oligonucleotide drugs, covering pharmacokinetics, immunogenicity, and pharmacodynamic/biomarker analysis. For pharmacokinetic characterization, BAS can select methods such as LC-MS/MS, LC-HRMS/LC-TOF-MS, LC-FLD, hybridization ELISA/MSD, qPCR, RT-qPCR, and ddPCR based on oligonucleotide length, modification type, analyte, sample matrix, and the need to distinguish metabolites. LC-MS/MS-based methods can provide strong structural selectivity to support parent drug and metabolite analysis, while hybridization- and PCR-based methods can offer highly sensitive solutions for low-abundance analytes or sequence-specific detection. Beyond pharmacokinetics, BAS can support immunogenicity assessment using a tiered strategy. It can also combine platforms such as RT-qPCR/ddPCR, enzyme-linked immunoassays, multiplex assays, and highly sensitive protein detection to support integrated assessments of gene expression modulation, downstream protein changes, and relevant biomarkers.
Summary and Outlook
Industry developments during the quarter show that oligonucleotide and related RNA therapies are advancing along different paths in specific diseases: ASOs have received new marketing approvals, muscle delivery programs have entered regulatory review, RNAi therapies are exploring dual-target designs and combination treatments for obesity, and mRNA therapies and in vivo base editing have provided new clinical evidence. Key areas to watch include the complete results of pivotal studies, the durability of effects with longer dosing intervals, and whether combination strategies and novel molecular designs can translate into further clinical benefits.
参考资料：
[1] 各家公司官方新闻稿
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