Randomised, Double-blind, Placebo-controlled Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (PRImus-AD)

Alzheimer's disease (AD) is the most common form of dementia. In the brains of people with AD, certain small substances stick together. This leads to changes in thinking and behaviour. The company PRInnovation is developing a new treatment for Alzheimer's disease, called PRI-002. It is thought that PRI-002 can cut the sticked substances back into small pieces. That would reduce the effects of Alzheimer's disease. In the current study the investigators examine whether PRI-002 is safe and effective in participants with mild cognitive impairment (MCI) or mild dementia due to AD.

开始日期2024-02-15

申办/合作机构

Prinnovation GmbH

[+2]

NCT04711486

/ Completed临床1期IIT

A Single-centre, Randomized, Placebo-controlled, Double-blind, Phase 1b Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Contraloid Acetate in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease

Patients with mild cognitive impairment due to Alzheimer's disease (MCI due to AD) are at high risk to develop Alzheimer´s dementia. The therapeutic agent Contraloid has the potential to influence the chronic neurodegenerative process of AD. As Contraloid was so far only administered to healthy subjects, the rational of the proposed study is first to collect safety data in patients diagnosed with MCI due to AD, as the absorption, distribution, metabolism and excretion processes may be altered by disease, aging, comorbidities and concomitant drug therapies. Additionally, the design of a subsequent phase II study will be based on the data of this study. The results of the exploratory analyses will enable power calculations and the identification of the most useful and reliable biomarkers for the subsequent proof of concept phase II study.

开始日期2020-12-08

申办/合作机构

Charité - Universitätsmedizin Berlin

[+1]

NCT03955380

/ Completed临床1期IIT

Single-center, Randomized, Prospective, Double-blind, Placebo Controlled Phase Ib Study With an Adaptive Multiple Ascending Dose (MAD) Design to Investigate the Safety, Tolerability, Pharmacokinetics of Contraloid Acetate (Healthy Subjects)

This is a single-center multiple-ascending-dose clinical trial assessing the safety and tolerability of oral dosing of Contraloid acetate in healthy volunteers. The study drug Contraloid (alias RD2, alias PRI-002) is an orally available all-D-peptide, which was developed to directly destroy toxic and replicating A-beta oligomer prions, by disassembling them into A-beta monomers. The study drug is specifically designed for the curative or at least disease-modifying treatment of cognition, memory and behavior deficits in Alzheimer´s disease patients. The study drug is BBB penetrable [1] and has demonstrated target engagement in vitro and in vivo [2, 3]. Treatments in three different transgenic mouse models in three different laboratories yielded improved cognition and deceleration of neurodegeneration, even under truly non-preventive treatment conditions and even when applied orally [2-5]. The hereby obtained PRI-002 plasma levels have also been achieved in humans after single oral dosing.

开始日期2018-12-12

申办/合作机构

Forschungszentrum Julich

[+5]

100 项与 PRI-002 相关的临床结果

登录后查看更多信息

100 项与 PRI-002 相关的转化医学

登录后查看更多信息

100 项与 PRI-002 相关的专利（医药）

登录后查看更多信息

项与 PRI-002 相关的文献（医药）

2026-06-01·CHEMISTRY-A EUROPEAN JOURNAL

A Chirality‐Guided Molecular Recognition Strategy for Targeting Intrinsically Disordered Proteins

Article

作者: Seguchi, Shiho ; Uchida, Satoru ; Tamura, Atsuo ; Hayashi, Ayaka ; Morita, Kenta ; Sugimoto, Kunihisa ; Chatani, Eri ; Miwa, Haruhiko ; Maruyama, Tatsuo

ABSTRACT:

Some peptide sequences are known to interact with their enantiomers to form stereocomplexes. However, the sequence‐dependent conditions required for stereocomplexation have not been thoroughly elucidated. Here, we present a systematic investigation of peptide stereocomplexation using short tripeptides and their enantiomers. Stereocomplexation was evaluated by aggregate formation in mixed aqueous solutions, and single‐crystal X‐ray diffraction revealed racemic crystals. Stereocomplexation was driven by hydrophobic interactions between phenylalanine residues and electrostatic interactions involving lysine and the C‐terminus. Thermodynamic and structural features of the complexation were further elucidated by calorimetry, simulations, and fluorescence assays. On the basis of these insights, a D‐peptide (Ac‐fffakr5‐NH 2 ) was rationally designed to target the –FFAE– motif of amyloid β42 (Aβ42), a pathological intrinsically disordered protein. This D‐peptide inhibited the fibrillization and cytotoxicity of Aβ42 in neuronal‐like cells, outperforming a clinical candidate, peptide drug RD2. These findings establish peptide stereocomplexation as a viable strategy for constructing sequence‐targeting ligands even against intrinsically disordered proteins.

2025-12-01·Alzheimers & Dementia

PRImus‐AD study: Design of the phase 2 study treating patients with MCI or mild dementia due to Alzheimer’s disease (AD) with the orally available PRI‐002

Article

作者: Brener, Alexander ; Tischler, Gerhard ; Kauselmann, Gunther ; Peters, Oliver ; Lindner, Katja ; Adermann, Knut ; Gabelich, Julie‐Anne ; Jürgens, Dagmar ; Willbold, Dieter ; Bartsch, Tina ; Zeiger, Kathrin

Abstract:

Background:

The drug candidate PRI‐002 is an all‐D‐enantiomeric peptide and was developed to disassemble toxic Aβ oligomers into harmless Aβ monomers. It is anticipated that PRI‐002 reduces neurotoxicity and restores synaptic plasticity in early stages of AD. In studies in healthy volunteers and in patients with mild cognitive impairment (MCI) and mild dementia due to AD (EudraCT 2020‐003416‐27) the orally administered PRI‐002 has demonstrated to be safe and well tolerable.

Method:

The PRImus‐AD study (EU clinical trial number 2022‐503148‐41) is a randomized, double‐blind, placebo‐controlled study to assess safety and efficacy of PRI‐002 in patients with MCI or mild dementia due to Alzheimer’s Disease (AD). The trial is conducted in six European counties at 40 study sites. The trial is registered at euclinicaltrials.eu/search‐for‐clinical‐trials/?lang=en&EUCT=2022‐503148‐41‐00 and clinicaltrials.gov/study/NCT06182085. CSF or Amyloid‐PET is used to confirm AD pathology. Stratification factors are disease state (MCI or mild dementia) and APOE e4 status. Eligible patients were randomly assigned (1:1:1) to receive 300 or 600 mg PRI‐002 per day or placebo following an adaptive design for 48 to 96 weeks of treatment duration. A follow‐up assessment is planned 12 weeks after the end of treatment. Besides to the endpoint of primary safety objectives the efficacy will be assessed by the change from baseline to week 48 in global outcome as measured by CDR‐SB.

Result:

540 patients in total were screened. Screening was accomplished three months ahead of the original schedule. A Screening Failure Rate of 42 % resulted in approx. 300 eligible patients (at the date of abstract submission) randomly assigned to 300 or 600 mg PRI‐002 per day or placebo. A blinded sample size recalculation confirmed the initial calculation of subjects to be enrolled. Although PRI‐002 is not expected to induce ARIAs, ARIA monitoring is closely performed for the first 90 patients until week 24.

Conclusion:

The PRIMUS‐AD phase 2 study will finally enroll about 300 patients with MCI and mild dementia due to AD to assess safety and therapeutic benefit of PRI‐002. Results are expected mid‐2026.

2025-07-01·ANTICANCER RESEARCH

Resveratrol Derivatives Inhibit Pro-survival Akt Signaling Pathway in Lung Cancer

Article

作者: NICHARAT SRIRATANASAK ; BHURICHAYA INNETS ; ZIN ZIN EI ; SATAPAT RACHA ; PITHI CHANVORACHOTE

BACKGROUND/AIM:

Akt signaling promotes cancer survival and therapy resistance. This study aimed to modify and improve resveratrol's efficacy by enhancing apoptosis induction in non-small cell lung cancer.

MATERIALS AND METHODS:

Molecular docking analysis was used to investigate the binding between resveratrol derivatives and the Akt protein. Western blot analysis evaluated the levels of apoptosis markers and signaling proteins.

RESULTS:

Resveratrol derivative, RD4 (4-(3-hydroxy-4-methoxyphenethyl)-2,6-dimethoxyphenol), shows binding potential to the allosteric site of Akt. After treatment of H460 cells with RD4 for 24 h, increased apoptosis and decreased levels of phosphorylated-Akt (p-Akt) protein were observed. Moreover, the levels of pro-apoptotic protein Bax and cleaved PARP were elevated, while those of the anti-apoptotic protein Bcl-2 were decreased. However, RD2 exhibited moderate effects at high concentrations and RD3 elevated p-Akt expression while exhibiting no apoptotic activity.

CONCLUSION:

RD4 suppresses Akt pathways by binding at the allosteric site of Akt. These findings provide a rationale for the design and optimization of novel Akt targeting agents for non-small cell lung cancer treatment.

项与 PRI-002 相关的新闻（医药）

2026-06-16

·尚霖学堂

第六集有关医学的前沿研究

我：老师，上集您讲了现有治疗方法，有对症的老药，也有靶向新药。但我知道科学探索从未停止——最近有什么让人振奋的新突破吗？老师：确实有很多令人兴奋的进展。我把它们分成五大方向来讲。 --- 方向一：修复血脑屏障——纳米技术逆转病情我：纳米技术？是那种微观级别的机器人吗？老师：可以这么理解。过去治疗思路是直接清除大脑里的“垃圾蛋白”，但效果有限且有副作用。川大华西医院等团队换了个思路——不直接清垃圾，而是修复“清洁系统”。他们发现血脑屏障上有一种叫LRP1的“运输受体”，负责把β-淀粉样蛋白运出去。但在患者体内这个受体几乎“消失”了。团队设计了一种叫A₄₀-POs的纳米技术，能精准引导LRP1走“运输通道”而非“降解通道”。效果惊人：注射后2小时内，小鼠脑内Aβ水平降低近45%；6个月后，相当于90岁高龄的小鼠恢复了健康小鼠的行为能力。研究团队说这就像激活了一个“正反馈机制”，让整个清理系统重新正常工作。我：相当于给大脑换了一套新的“排污管道”？老师：对。而且不只是清除垃圾，是修复了整个血管系统的功能。方向二：绘制“疾病地图”——UCLA的四条路径我：这又是什么？老师：UCLA分析了近2.5万名患者的健康数据，发现阿尔茨海默病不是一条路走到黑，而是有四条不同的发展路径： · 心理健康路径：抑郁症等精神问题逐渐导致认知下降 · 脑病路径：脑功能障碍逐步加重 · 轻度认知障碍路径：认知能力逐渐下降 · 血管疾病路径：高血压等心血管问题我：这意味着不同的人可能需要不同的预防方案？老师：正是。以前是“一刀切”，现在可以根据每个人的风险路径量身定制预防方案。比如研究发现约26% 的病例遵循可预测的健康序列——高血压通常出现在抑郁症之前，这种组合比单一疾病风险更高。方向三：从源头阻止——新药研发多点开花我：除了仑卡奈单抗这些，还有新药吗？老师：2025年AD药物开发管线包含182项临床试验，评估138种新型药物。几个亮点： Tau蛋白抑制剂——tau缠结与认知衰退关系更直接，但药物需穿越血脑屏障。礼来已投入10亿美元研发，Oligomerix的口服药OLX-07010已进入I期临床且安全性良好。铜基药物——澳大利亚团队发现Cu(ATSM)能修复大脑“排污泵”，56天治疗让小鼠脑内Aβ减少42%，空间学习能力提高44%。该药已在帕金森病中做过安全测试。 Aβ寡聚体靶向药——PRI-002已进入II期临床试验。脑修复免疫药——通过激活外周免疫系统帮助大脑自我修复，早期结果显示安全性良好。方向四：一滴血预测——早期筛查的革命我：这是不是意味着以后抽个血就能知道风险？老师：没错。2025年《Nature Medicine》研究证实，将 “Aβ42/Aβ40比值 + p-tau217 + NfL” 三个标志物组合检测，对AD临床前期的识别准确率超过90%。我：临床前期是什么意思？老师：就是症状出现前5到10年。这项研究追踪了3200人5年，发现标志物阳性且携带APOE ε4基因的人，发展为轻度认知障碍的风险是普通人的11倍。而且费用仅为PET检查的1/20。我：这太有意义了——知道自己高风险，就可以提前干预！老师：对。这就是从“对症治疗”向 “预防为先” 转变的关键。方向五：更深层的机制探索我：科学家还在研究什么？老师：比如ABCA7基因——2025年《Nature》研究首次阐明这个基因变异如何通过影响脂质代谢驱动疾病。还有OTULIN蛋白——研究发现它竟是一个控制tau蛋白是否产生的“总开关”。另外中科院团队开发了Tau清除细胞疗法，用工程化单核细胞主动进入大脑清除有毒的Tau蛋白。我：老师，听完这些我特别振奋——原来科学界正在从那么多角度同时进攻这个病！老师：是的。虽然现在还无法说“治愈”，但预防、早期筛查、精准干预这条路径已经越来越清晰。正如UCLA所说，这些突破正在彻底改变我们应对阿尔茨海默病的方式。我：太好了！那下一集，我们就回到最落地的话题——中医“治未病”，具体怎么做预防？老师：好，我们下一集见。

2026-04-22

·丁香园神经时间

APOE4 高风险人群如何破局？一文读懂阿尔茨海默病诊疗现状与研发新进展

引言阿尔茨海默病（简称 AD）是一种常见的神经退行性疾病，主要表现为记忆力下降、认知功能减退、行为异常，以及日常生活能力逐渐丧失。在我国，65 岁以上人群中 AD 患病率已达 6.0%，约每 17 人就有 1 人患有 AD，疾病负担远超全球平均水平 [1]。在临床上，AD 的两大核心病理特征是：大脑中出现 β-淀粉样蛋白（Aβ）沉积形成的「斑块」，以及 tau 蛋白过度磷酸化形成的「神经纤维缠结」[1]。但长期以来，AD 的治疗只能暂时缓解症状，无法延缓疾病进展。近年来，靶向 Aβ 的单克隆抗体药物取得了突破，但仍面临疗效争议、安全风险和临床应用不便等挑战 [2-3]。如何开发更安全、更有效、更方便的新疗法，已成为全球 AD 药物研发的核心目标。 AD 机制研究不断深入，精准生物标志物仍需突破 AD 的发病机制非常复杂，至今尚未明确。对于 AD 的发病机制的研究，目前较为公认的包括「Aβ 假说」和「tau 蛋白假说」。「Aβ 假说」认为，Aβ 生成过多或清除不足是 AD 的关键驱动因素。在 Aβ 形成斑块之前，可溶性的 Aβ 寡聚体会损伤神经元之间的连接（突触），并产生神经毒性 [2]。而「tau 蛋白假说」则强调，过度磷酸化的 tau 蛋白在神经细胞内形成神经纤维缠结，也是 AD 的标志性病理改变之一 [2]。除了上述机制，遗传因素也扮演重要角色。载脂蛋白 E ε4（APOE ε4）是目前已知 AD 最常见的遗传风险基因，约 50% 的散发性 AD 病例与之相关 [2]。携带一个 APOE ε4 拷贝的个体，患病风险高于非携带者；携带两个拷贝（即纯合子）的个体，患病风险则更高 [2]。APOE ε4 携带者脑内 Aβ 和 tau 蛋白的异常积聚速度更快，认知功能下降和海马体（大脑的记忆中枢）萎缩也更早出现 [8]，因此这类患者面临更为迫切的治疗需求。图 1：AD 核心病理机制和遗传风险基因 [2] 诊断方式上，在精准医疗时代，AD 的诊断正从单纯看症状，转向采用生物标志物（可测量的生物学指标）进行精准判断 [1]。目前，通过腰椎穿刺获取脑脊液并检测生物学标志物（如 Aβ42/Aβ40 比值、p-tau181/Aβ42 比值）具备高诊断准确性，但受限于穿刺取样的有创性，难以大规模推广 [1]。相比之下，血液生物标志物检测（如血浆 Aβ42/Aβ40 比值、血浆 p-tau217 等）操作简便、创伤小，更适合大规模筛查。目前，血浆 Aβ42/Aβ40 比值和血浆 p-tau217 等血液生物指标，已可用于 AD 的早期筛查与疗效监测，为更早发现疾病、更早干预提供了有力工具。更多新型标志物和影像学指标仍在持续研究中。 AD 治疗进入「疾病修饰」阶段，新药选择仍待丰富过去很长时间里，AD 的治疗主要依赖两类传统药物：胆碱酯酶抑制剂和 NMDA 受体拮抗剂 [4]，但这些药物都只能暂时改善症状，无法改变疾病进程 [3]。近些年，两款靶向清除脑内 Aβ 的新型单抗药物相继在国内外获批，标志着 AD 治疗进入了疾病修饰治疗（DMT）的新阶段，即能够延缓疾病进展、改变病程的疗法 [1,4]。研究显示，抗 Aβ 单抗可以显著降低大脑中的 Aβ 负荷，有效延缓认知和功能衰退 [3,5]。然而这类药物可能引起 Aβ 相关影像异常（ARIA），主要表现为伴有水肿的 ARIA（ARIA-E）和伴有含铁血黄素沉积的 ARIA（ARIA-H）。ARIA 通常无症状，但有极小的可能发生罕见的严重事件 [3-4]。研究还发现，ARIA 的发生与 APOE 基因型密切相关。其说明书提示，与 ApoE ε4 杂合子和非携带者相比，接受抗 Aβ 单抗治疗的 ApoE ε4/4 纯合子患者的 ARIA 发生率更高，包括症状性和严重 ARIA [3-4]。抗 Aβ 疗法的获批是 AD 治疗领域的一个重要里程碑，但临床上仍需更多新型疾病修饰药物，以丰富治疗用药选择。 AD 药物研发新格局：多条路径齐头并进如今，AD 新药研发呈现出多元化格局：从口服小分子抑制剂、下一代抗体，到靶向 Aβ、tau 蛋白以及神经保护机制，多条路径同步推进。一、靶向 Aβ 的新一代疗法由于抗 Aβ 单抗治疗存在 ARIA 风险，且需要静脉输注给药，不够便捷，推动了口服小分子 Aβ 抑制剂的研发热潮兴起。这类药物旨在从 Aβ 级联反应的上游进行干预，阻止 Aβ 单体错误折叠和聚集 [6]。 01 从希望到转折，ALZ-801 研发带来新启示 ALZ-801 是高牛磺酸的前体药物，通过抑制 Aβ42 寡聚体形成发挥作用 [6]。在针对 APOE ε4/4 纯合子和杂合子早期 AD 患者的 Ⅱ 期试验中，该药表现良好：84 例患者治疗 2 年后，血浆 p-tau181 水平显著降低 31%（P = 0.045），海马萎缩得到缓解，且整个研究期间未观察到血管源性脑水肿事件 [7]。 APOE ε4 携带者因基因原因，Aβ 和 tau 病理加速沉积、认知下降更快、海马萎缩更严重，治疗需求尤为迫切。上述 ALZ-801 的 Ⅱ 期研究结果，曾为这部分患者带来治疗的希望 [8]。然而，2025 年公布的 Ⅲ 期 APOLLOE4 研究结果却增添了不确定性 [9]。在 325 例早期 AD 患者（均为 APOE ε4/4 纯合子，包括轻度认知障碍和轻度 AD）中，ALZ-801 治疗 78 周后，主要认知终点（ADAS-Cog13 量表）未能达到统计学显著性（仅延缓 11%，P = 0.607）[9]。尽管在总体人群中未达到主要认知终点，但预设的亚组分析中却出现了令人振奋的不同结果：在轻度认知障碍（MCI）亚组（125 例）中，ALZ-801 展现出显著且一致的临床获益，认知衰退延缓（ADAS-Cog13）52%（P = 0.041），日常功能衰退（痴呆残疾评估量表）延缓 96%（P = 0.016）[9]。这意味着，在更早期的 MCI 阶段就开始用药的患者，认知功能衰退被有效延缓了一半以上。图 2：MCI 亚组中认知功能和日常生活能力获益显著 [9] 更值得关注的是，部分患者在治疗 78 周后，海马体积不仅没有萎缩，反而出现了增长，这类患者被称为「超级应答者」[10-11]。在 APOLLOE4 研究中，活性药物治疗组有 16% 的患者属于超级应答者，而安慰剂组只有 3%[10]。与整体早期 AD 人群相比，这些超级应答者年龄更小、基线认知评分更高、基线海马体积更大[10]，提示早期干预可能是 APOE ε4/4 纯合子实现疾病修饰治疗获益的关键。随后公布的 ALZ-801 4 年开放标签扩展研究结果，为这份临床获益提供了坚实的长期证据[8]：在该研究的 MCI 亚组中，APOE ε4/4 纯合子携带者经 ALZ-801 治疗 4 年后，认知状态（MMSE 评分）稳定的比例高达 67%（8/12），而 APOE ε3/4 杂合子携带者中这一比例仅为 46%（6/13）[8]。 02 国内创新药 RP902：直接瞄准获益优势人群——MCI 患者 RP902 是润佳医药自主研发的小分子 Aβ 抑制剂，与 ALZ-801 类似，均在牛磺酸结构基础上优化，但 RP902 是氘代高牛磺酸的前体药物，体内转化为氘代高牛磺酸后起效，进一步优化了药代动力学特性[12]。RP902 可抑制大脑中与 AD 患者认知功能下降直接相关的可溶性 Aβ 寡聚体的形成，消除或降低 Aβ 对神经细胞的毒性，对血脑屏障损伤也有一定的缓解和保护作用[12-13]。该药于 2022 年 12 月获得中国 NMPA 临床试验批件，是我国首个进入临床试验的小分子 Aβ 抑制剂[13]。临床前研究显示，RP902 在 AD 模型小鼠中能改善形象识别记忆、空间记忆和长期记忆障碍，降低 Aβ 沉积以及可溶性和不溶性 Aβ1-40/1-42 水平。目前，RP902 已完成 Ⅰ 期临床研究，其 Ⅱ/Ⅲ 期试验已获 CDE 批准，针对携带 APOE ε4 等位基因的阿尔茨海默病源性 MCI 阶段患者，临床正在启动中 [14]。 03 其他口服小分子 PRI-002（RD2）：通过将 Aβ 寡聚体分解为单体，降低神经毒性，恢复突触可塑性，目前处于 Ⅱ 期临床阶段[15-16]。 ALX-001 / BMS-9894923：通过阻断 Aβ 与 mGluR5 相互作用，防止突触丢失，Ⅰ 期试验进行中[17]。 04 下一代抗 Aβ 单抗新一代抗体致力于解决现有药物的局限性 [18]。 Trontinemab：利用转铁蛋白受体技术实现跨血脑屏障转运，提高脑内药物浓度，Ⅲ 期临床正在招募[19-20]。 Remternetug：多奈单抗的后续产品，支持皮下注射，给药更便捷，Ⅱ/Ⅲ 期研究进行中[18,21]。 Sabirnetug：选择性靶向可溶性 Aβ 寡聚体，Ⅰ 期已完成，Ⅱ 期研究招募中[22-23]。二、靶向 Tau 蛋白的药物由于 tau 蛋白病理负荷与 AD 认知下降密切相关，靶向 tau 的治疗正成为研发热点 [5]。 Bepranemab：抗 tau 单抗，Ⅱ 期临床已完成 [5,24]。 BIIB080（MAPTRx）：首款靶向 tau 的反义寡核苷酸药物，通过抑制 tau 蛋白生成发挥作用。Ⅰb 期探索性分析显示认知和功能下降速度持续减缓，Ⅱ 期研究进行中 [25]。三、神经保护机制疗法这类策略旨在支持神经元存活、增强突触可塑性，延缓神经退行性变。但这一方向的临床有效性仍需大型随机对照研究验证。 AR1001：口服 PDE5 抑制剂，通过提高细胞内 cGMP 水平，激活下游信号通路，从而增强突触可塑性并促进神经细胞存活。该药的 Ⅱ 期临床试验未达主要终点，Ⅲ 期临床试验正在进行中 [26]。 GSK4527226（AL101）：靶向 sortilin 的单抗，通过调节小胶质细胞功能增强对 Aβ 和 tau 的清除，Ⅱ 期进行中 [27]。四、其他前沿方向基因疗法：针对 APOE4 的多重策略——包括靶向抗体清除有害蛋白、病毒载体导入保护性 APOE2 基因、CRISPR 基因编辑降低 APOE4 表达等，均处于临床前或早期临床阶段 [5]。主动免疫疫苗： ACI-24.060：靶向 Aβ，诱导针对 Aβ 寡聚体和原纤维的多克隆抗体应答，Ⅰb/Ⅱ 期研究正在进行中 [28]。 ACI-35.030 和 JACI-35.054：靶向磷酸化 tau 蛋白的脂质体疫苗，通过诱导针对病理性 tau 的免疫应答，阻止 tau 聚集，Ⅰb/Ⅱa 期临床试验数据支持诱导更快速持久的 ACI-35.030 进入下一阶段 Ⅱb 期临床研究阶段 [29]。结语：精准预防与早期干预，AD 治疗的新希望随着血液生物标志物的普及和疾病修饰疗法的问世，AD 药物研发正从「症状期干预」向「临床前阶段预防」前移 [4]。目前已有多个临床试验在探索这一策略。小分子 Aβ 抑制剂凭借良好的安全性和口服便捷性，在破解 APOE ε4 携带者（高风险人群）的治疗困境方面展现出巨大潜力 [8-11]。未来，通过高灵敏度的血液生物标志物精准识别高危个体，在神经元尚未发生不可逆损伤的临床前阶段，采用安全、便捷的口服药物进行早期干预，有望从源头上延缓甚至阻止 AD 的发生。将干预窗口前移至临床前阶段，结合生物标志物指导的精准预防，已成为 AD 领域值得期待的发展方向。 ✩ 本文仅供医疗卫生等专业人士参考内容策划：郭青青项目审核：唐静题图来源：图虫创意参考文献 [1] 中国微循环学会神经变性病专业委员会, 王盼, 刘帅, 等. 阿尔茨海默病诊断规范共识 [J]. 中国现代神经疾病杂志,2026,26(02):112-128. [2] Fu C, Li X, Liu X, et al. Psychoactive substances: novel molecular insights and therapeutic potential for Alzheimer's disease. Transl Neurodegener. 2025 Jul 25;14(1):38. [3] 刘雨辉, 卜先乐, 马辛, 等. 阿尔茨海默病药物治疗指南 [J]. 阿尔茨海默病及相关病杂志,2025,8(01):8-16. [4] Wu CK, Fuh JL. A 2025 update on treatment strategies for the Alzheimer's disease spectrum. J Chin Med Assoc. 2025 Jul 1;88(7):495-502. [5] Guo X, Yue R, Cui Z, et al. Advances of therapeutic strategies for Alzheimer's disease. J Neurol. 2025 Oct 17;272(10):705. [6] Hey JA, Kocis P, Hort J, et al. Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that InhⅠbits Beta Amyloid Oligomer Formation in the Human Brain. CNS Drugs. 2018 Sep;32(9):849-861. [7] Hey JA, Abushakra S, Blennow K,et al. Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease. Drugs. 2024 Jul;84(7):811-823. [8] J Patrick Kessiak, et al. Biomarker-Positive APOE4 Carriers with MCI Show Disease Stability over 4-Years of Valiltramiprosate/ALZ-80I Treatment: MMSE Responder Analysis from the ALZ-801 Phase 2 Long-Term Extension Study. Poster 01 326. Presented at AD/PD 2026. [9] Abushakra S, Power A, Watson D, et al. Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEε4/ε4 Homozygotes with Early Alzheimer's Disease: Results of the Phase III, Randomized, Double-Blind, Placebo-Controlled, 78-Week APOLLOE4 Trial. Drugs. 2025 Nov;85(11):1455-1472. [10] Jeremy Yu,et al. VALILTRAMIPROSATE REVERSES NEURODENEGERATION AND IMPROVES CLINICAL OUTCOMES IN SUBGROUP OF EARLY SYMPTOMATIC AD IN HOMOZYGOTES: RESULTS FROM 78 WEEK PHASE 3 APOLLOE4 TRIAL. ID:1299. Presented at AD/PD 2026. [11] Jeremy Yu,et al. Valiltramiprosate/ALZ-801 Prevents Hippocampal Atrophy and Clinical Decline in a Stage 2 AD Subpopulation in APOLLOE4 Phase 3 Study. Presented at AD/PD 2025. [12] 润佳医药官网. RP902 临床开发.http://www.risen-pharma.com/clinical/id-2.html [13] 润佳医药科技公众号. 重磅 | 润佳医药 RP902（靶向 Aβ）临床试验申请获得中国 NMPA 批准. https://mp.weixin.qq.com/s/JFsPorNIA-tmH-k9dwoG4A [14] 药物临床试验登记与信息公示平台. https://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml [15] Kutzsche J, Cosma NC, Kauselmann G, et al. Oral PRI-002 treatment in patients with MCI or mild AD: a randomized, double-blind phase 1b trial. Nat Commun. 2025 May 6;16(1):4180. [16] ClinicalTrials. Study to Assess Safety and Efficacy of PRI-002 in Patients With MCI to Mild Dementia Due to Alzheimer's Disease (AD) (PRImus-AD). NCT06182085. [17] ClinicalTrials. A Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates. NCT06632990. [18] Rafii MS, Aisen PS. Amyloid-lowering immunotherapies for Alzheimer disease: current status and future directions. Nat Rev Neurol. 2025 Sep;21(9):490-498. [19] Grimm HP, Schumacher V, Schäfer M, et al. Delivery of the Brainshuttle™ amyloid-beta antⅠbody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans. MAbs. 2023 Jan-Dec;15(1):2261509. [20] ClinicalTrials. A Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (TRONTIER 1). NCT07169578 [21] ClinicalTrials. A Study of a Potential Disease Modifying Treatment in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation (DIAN-TU-002). NCT06647498 [22] Cline EN, Antwi-Berko D, Sundell K, et al. Biofluid biomarker changes following treatment with sabirnetug (ACU193) in INTERCEPT-AD, a phase 1 trial in early Alzheimer's disease. J Prev Alzheimers Dis. 2025 Apr;12(4):100082. [23] ClinicalTrials. A Study to Evaluate Efficacy and Safety of Intravenous Sabirnetug in Participants With Early Alzheimer's Disease (ALTITUDE-AD) (ALTITUDE-AD). NCT06335173 [24] ClinicalTrials. A Study to Test the Efficacy, Safety, and Tolerability of Bepranemab (UCB0107) in Patients With Mild Cognitive Impairment or Mild Alzheimer's Disease (AD). NCT04867616 [25] Shulman M, Wu S, Ziogas N,et al. Exploratory analyses of clinical outcomes from the BIⅠB080 phase 1b study in mild Alzheimer's disease. Nat Aging. 2026 Feb;6(2):445-453. [26] Greeley D, Nash M, Herskowitz B, et al. A phase 2 randomized, placebo-controlled study on the efficacy and safety of AR1001, a phosphodiesterase-5 inhⅠbitor, in patients with mild-to-moderate Alzheimer's disease. J Prev Alzheimers Dis. 2025 Nov;12(9):100337. [27] Budda B, Mitra A, Park L, et al. Development of AL101 (GSK4527226), a progranulin-elevating monoclonal antⅠbody, as a potential treatment for Alzheimer's disease. Alzheimers Res Ther. 2025 Jul 25;17(1):174. [28] ClinicalTrials. A Study to Assess the Effects of ACI-24.060 in Alzheimer's Disease and in Down Syndrome (ABATE Study). NCT05462106 [29] Sol O, Mermoud J, Hallikainen M, et al. Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study. EBioMedicine. 2025 Oct;120:105940.

2026-04-10

·QQ浏览器

第一季度，多肽疗法迎来多项新进展，治疗肥胖、糖尿病、“脂肪肝”、肾病等

编者按：近年来，凭借代谢稳定性高、靶点亲和力强以及生物特异性优异等优势，多肽疗法正迅速崛起为全球新药研发的重要方向。从GLP-1类代谢疾病疗法持续取得突破，到肿瘤、神经系统疾病及免疫疾病等领域不断涌现的新型多肽分子，多肽药物的研发版图正在不断拓展。为了更好地满足全球合作伙伴的研发需求，药明康德围绕多肽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，并提供药代动力学分析和免疫原性检测等整合生物分析解决方案，为发现和开发多肽及复杂多肽偶联药物提供有力支持。本文将盘点2026年第一季度全球多肽疗法在监管审批、临床研究以及产业合作等方面的重要进展，并结合相关技术挑战，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年第一季度，多肽疗法在全球范围内迎来多项重要监管进展。其中，GLP-1类疗法继续在肥胖及相关疾病领域取得突破。诺和诺德（Novo Nordisk）高剂量司美格鲁肽Wegovy HD（7.2 mg）注射剂在本季度获得美国FDA批准，用于已耐受2.4 mg剂量治疗至少4周、且仍需进一步减重的肥胖患者。与此同时，司美格鲁肽（商品名Kayshild）获得欧洲药品管理局（EMA）人用药品委员会（CHMP）推荐有条件批准，用于治疗伴有肝纤维化的非肝硬化性代谢功能障碍相关脂肪性肝炎（MASH），预计将在今年4月正式获批。根据新闻稿介绍，Kayshild有望成为首个获EMA批准用于MASH适应症的GLP-1类药物。此外，加拿大卫生部（Health Canada）在今年1月批准司美格鲁肽口服片剂（商品名Rybelsus），用于降低患有2型糖尿病且已确诊心血管疾病或具有高心血管风险的成人患者发生主要不良心血管事件（MACE，包括心血管死亡、非致死性心肌梗死或非致死性卒中）的风险。在非GLP-1类疗法方面，多款多肽药物也取得关键监管突破。Ascendis Pharma旗下Yuviwel（navepegritide；TransCon CNP）获得美国FDA加速批准，用于治疗2岁及以上且骨骺尚未闭合的软骨发育不全儿童。根据公司新闻稿，该药物为首个获批用于该患者人群、且每周一次给药的治疗方案。图片来源：123RF同样在3月，强生（Johnson & Johnson）与Protagonist Therapeutics公司联合开发的口服多肽疗法Icotyde（icotrokinra）获得FDA批准，用于一线治疗中重度斑块状银屑病（PsO）成人患者，以及12岁及以上、体重至少40 kg且适合接受全身治疗或光疗的儿童患者。根据新闻稿，Icotyde是首个能够精准阻断IL-23受体的靶向口服多肽药物。此外，Rhythm Pharmaceuticals旗下多肽药物Imcivree（setmelanotide）的扩展适应症也在本季度获得FDA批准，用于治疗成人及4岁及以上儿童获得性下丘脑性肥胖（HO），以降低过多体重并长期维持减重效果。同样值得关注的是，欧盟委员会（EC）批准Sobi与Apellis Pharmaceuticals联合开发的Aspaveli（pegcetacoplan），用于与肾素-血管紧张素系统（RAS）抑制剂联合治疗12至17岁青少年及成人C3肾小球病（C3G）或原发性免疫复合物型膜增生性肾小球肾炎（IC-MPGN）。临床进展在临床研究方面，GLP-1相关疗法仍是本季度多肽研发最活跃的领域之一，多家药企在肥胖及代谢疾病治疗方向持续取得进展。礼来（Eli Lilly and Company）宣布，其潜在“first-in-class”三重激素受体激动剂retatrutide在3期试验中取得积极结果。该分子可同时靶向葡萄糖依赖性促胰岛素多肽（GIP）、胰高血糖素样肽-1（GLP-1）以及胰高血糖素受体。研究分析显示，2型糖尿病患者在接受每周一次retatrutide治疗40周后，糖化血红蛋白（A1C）平均下降1.7–2.0个百分点，而最高剂量组患者的平均体重下降达到16.8%（36.6磅）。与此同时，辉瑞（Pfizer）的长效GLP-1受体激动剂PF-08653944（PF'3944，曾用名MET-097i）也在2b期试验中取得积极结果。研究显示，所有四种剂量方案在主要终点——从随机分组至第28周的体重降低——方面均显著优于安慰剂（P<0.001）。值得关注的是，在切换至每月给药后，减重效果依然强劲且持续，在第28周尚未出现平台期，提示该疗法具备每月一次给药的潜力。目前，PF'3944的多项3期试验正在推进中。此外，Viking Therapeutics旗下GIP/GLP-1双重受体激动剂VK2735的2期试验结果发表于《肥胖》期刊，其3期试验也在本季度完成患者招募。Altimmune旗下候选药物pemvidutide则在今年年初获得FDA突破性疗法认定，用于治疗MASH。公司已与FDA就3期注册试验关键设计达成一致，即将启动针对中至重度肝纤维化MASH患者的3期研究。与此同时，诺和诺德宣布其固定剂量联合疗法CagriSema在3期试验中，在减重与改善A1C方面均优于司美格鲁肽。CagriSema由长效胰淀素类似物cagrilintide（2.4 mg）与司美格鲁肽（2.4 mg）组成。此外，Zealand Pharma与艾伯维（AbbVie）旗下的胰淀素靶向疗法petrelintide与ABBV-295也在本季度分别公布了用于治疗肥胖患者的2期与1期试验积极结果。值得注意的是，GLP-1疗法的应用范围正在逐步拓展至代谢疾病之外。礼来在本季度宣布，其GLP-1/GIP双重受体激动剂Zepbound（tirzepatide）联合IL-17A单抗Taltz（ixekizumab），在两项分别针对中重度斑块状银屑病及活动性银屑病关节炎（PsA）肥胖或超重患者的3期试验中均达到主要终点。这些结果显示，GLP-1类疗法有望与银屑病生物制品形成新的联合治疗策略。除GLP-1相关疗法外，本季度多项多肽疗法也在其他疾病领域取得进展。例如，Priavoid旗下靶向β-淀粉样蛋白（Aβ）寡聚体的口服多肽疗法PRI-002在2期试验中显示，其淀粉样相关影像学异常（ARIA）发生率与既往3期研究中安慰剂组水平相当。此外，一项1/2期试验结果显示，一名同时患有家族性腺瘤性息肉病（FAP）及相关硬纤维瘤的患者在接受Parabilis Medicines潜在“first-in-class”多肽疗法zolucatetide治疗60周后，十二指肠息肉病变显著改善。与治疗前评估相比，该患者息肉数量和大小均明显减少，疾病分期由Spigelman II期降至I期，同时硬纤维瘤直径减少了52.2%。根据新闻稿，zolucatetide是首个直接抑制β-catenin与TCF相互作用的抑制剂。研发合作与融资进展在产业合作方面，本季度多家大型药企围绕多肽疗法达成金额达数亿美元甚至数十亿美元的合作协议。今年1月，阿斯利康（AstraZeneca）与石药集团达成最高可达35亿美元的战略合作，双方将共同推进覆盖肥胖症与2型糖尿病的8项下一代疗法研发。根据协议，双方将首先推进其中4个项目，这些项目将结合石药集团AI驱动的肽类药物发现平台以及其专有的LiquidGel每月一次给药平台技术。此外，诺华（Novartis）在2月与Unnatural Products（UNP）达成总金额超过17亿美元的大环肽合作，进一步加码这一新兴分子领域。融资方面，多家创新公司也获得资本市场支持。Parabilis Medicines在今年初完成超过3亿美元的F轮融资，所获资金将用于推进zolucatetide的开发。同时，峰肽药业（Pinnacle Medicines）也于3月时完成8900万美元的B轮融资，用于加速管线的临床推进。▲2026年第一季度多肽药物领域部分投融资信息一体化平台助力多肽药物创新随着多肽疗法在肥胖、代谢疾病以及更多创新适应症中的研发不断推进，其分子设计也正变得愈发复杂。从脂肪酸修饰、PEG化，到蛋白融合与多肽偶联等策略，越来越多的新一代多肽分子通过结构改造实现更长半衰期或更优药效。然而，这些创新设计在带来治疗潜力提升的同时，也对药物开发过程中的生物分析提出了更高要求。特别是在临床研究阶段，如何准确解析多肽药物的体内暴露特征、免疫原性风险以及结构修饰带来的影响，已成为推动相关疗法顺利进入后期开发的重要基础。在这一趋势下，能够同时支持药代动力学（PK）与免疫原性评价的系统化生物分析能力，正成为创新多肽药物研发的重要技术支撑。为帮助合作伙伴更好地应对这些挑战，药明康德生物分析部（BAS）依托高度成熟的生物分析技术平台，构建了面向新一代多肽药物开发需求的系统化分析解决方案，能够有效应对多肽分子在临床试验中药代动力学与免疫原性研究的复杂挑战。随着多肽药物分子量增加、结构修饰增多及偶联形式日益复杂，其生物分析面临一系列特有挑战。例如，一方面，多肽在液相色谱串联质谱（LC-MS/MS）分析中通常呈现多电荷态分布及电离效率不均一，导致信号分散与离子抑制，从而影响检测灵敏度与方法稳健性；另一方面，多肽分子表位有限且与内源性肽序列高度同源，往往表现为免疫原性较低、特异性抗体制备困难，同时在配体结合分析（LBA）中易出现内源性干扰与交叉反应，增加免疫原性评价的复杂性。此外，脂肪酸修饰、PEG化或蛋白融合等结构改造在延长半衰期的同时，也可能引入新的免疫原性风险（如抗PEG抗体），对抗药抗体（ADA）与中和抗体（NAb）检测提出更高要求。针对上述行业痛点，药明康德生物分析部整合高灵敏度LC-MS/MS、免疫捕获-质谱、ELISA/MSD平台及细胞功能分析方法，实现PK分析、抗药抗体（ADA）与中和抗体（NAb）评价的一体化支持。通过优化样本前处理策略、建立免疫捕获-质谱联用技术及基于胰蛋白酶消化的bottom-up分析方法，可显著提升检测灵敏度并降低基质干扰，在复杂修饰多肽及长链多肽分析中表现出良好的方法特异性与稳健性。同时，针对多肽药物免疫原性评价中的低免疫原性与高同源性带来的检测难点，团队建立了分层（tiered）免疫原性评价体系，整合桥式（bridging）ADA检测、确认实验及滴度分析，并结合酸解离（ACE）、MRD优化等策略提升药物耐受性与检测灵敏度；通过优化标记试剂设计及方法学条件，有效降低内源性干扰与非特异性结合，并结合细胞功能性NAb分析方法，实现从ADA筛查到中和效应评价的全流程覆盖，从而系统性支持复杂修饰多肽及偶联多肽药物的免疫原性风险评估。药明康德生物分析技术平台已成功支持GLP-1类似物、胰岛素类似物等新一代多肽药物的临床PK研究及免疫原性评估，形成覆盖方法开发、验证到样本检测的端到端能力。依托标准化流程与多技术协同优势，药明康德生物分析部能够为合作伙伴提供高灵敏度、高可靠性的多肽药物生物分析支持，加速创新多肽疗法从研究阶段迈向临床开发。Multiple FDA Approvals and Hundreds of Millions in Investments: Peptide Therapeutics See Significant Progress in Q1In recent years, peptide therapeutics have rapidly emerged as a major direction in global drug discovery, driven by their high metabolic stability, strong target affinity, and excellent biological specificity. From continued breakthroughs in glucagon-like peptide-1 (GLP-1)–based therapies for metabolic diseases to the emergence of novel peptide molecules targeting oncology, neurological disorders, and immune diseases, the landscape of peptide drug development continues to expand. To better meet the evolving needs of global partners, WuXi AppTec has established an integrated solution for peptides and related chemical conjugates, covering key stages including custom synthesis, covalent conjugation, process development, and CMC, while also providing integrated bioanalytical solutions such as pharmacokinetic analysis and immunogenicity assessment. Together, these capabilities provide strong support for the discovery and development of peptides and complex peptide conjugate therapeutics.This article reviews major developments in peptide therapeutics worldwide during the first quarter of 2026, including regulatory approvals, clinical progress, and industry collaborations, while highlighting key technical challenges and emerging trends shaping this rapidly evolving field.Regulatory DevelopmentsIn the first quarter of 2026, peptide therapeutics achieved several important regulatory milestones globally. Among them, GLP-1 therapies continued to make breakthroughs in obesity and related disease areas. Novo Nordisk’s high-dose semaglutide Wegovy HD (7.2 mg) injection received U.S. FDA approval this quarter for obesity patients who have tolerated the 2.4 mg dose for at least four weeks but still require additional weight reduction.Meanwhile, semaglutide (brand name Kayshild) received a recommendation for conditional approval from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis in patients without cirrhosis. The therapy is expected to receive formal approval in April this year. According to the company, Kayshild could become the first GLP-1 therapy approved by the EMA for a MASH indication.In addition, Health Canada approved the oral semaglutide tablet Rybelsus in January for reducing the risk of major adverse cardiovascular events (MACE)—including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke—in adults with type 2 diabetes who have established cardiovascular disease or are at high cardiovascular risk.Beyond GLP-1 therapies, several peptide drugs also achieved key regulatory breakthroughs. Yuviwel (navepegritide; TransCon CNP) from Ascendis Pharma received accelerated approval from the U.S. FDA for the treatment of children aged two years and older with achondroplasia whose growth plates have not yet closed. According to the company, the drug is the first once-weekly treatment approved for this patient population.Also in March, oral peptide therapy Icotyde (icotrokinra) developed by Johnson & Johnson in collaboration with Protagonist Therapeutics received FDA approval as a first-line treatment for adults with moderate-to-severe plaque psoriasis (PsO), as well as pediatric patients aged 12 years and older weighing at least 40 kg who are eligible for systemic therapy or phototherapy. According to the press release, Icotyde is the first targeted oral peptide drug designed to selectively block the IL-23 receptor.Additionally, Rhythm Pharmaceuticals’ peptide drug Imcivree (setmelanotide) received FDA approval this quarter for an expanded indication to treat acquired hypothalamic obesity (HO) in adults and children aged four years and older, helping reduce excess body weight and maintain long-term weight loss.Meanwhile, the European Commission (EC) approved Aspaveli (pegcetacoplan) developed by Sobi and Apellis Pharmaceuticals for use in combination with renin-angiotensin system (RAS) inhibitors to treat adolescents aged 12–17 and adults with C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).Clinical ProgressIn clinical development, GLP-1–related therapies remained one of the most active areas of peptide drug research this quarter, with several pharmaceutical companies reporting progress in obesity and metabolic disease treatments. Eli Lilly and Company announced positive Phase 3 results for its potential first-in-class triple hormone receptor agonist retatrutide, which simultaneously targets GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Analysis showed that after 40 weeks of once-weekly treatment, patients with type 2 diabetes experienced an average HbA1c reduction of 1.7%–2.0%, while patients in the highest-dose group achieved an average body-weight reduction of 16.8% (36.6 lbs).At the same time, Pfizer’s long-acting GLP-1 receptor agonist PF-08653944 (PF'3944, formerly MET-097i) demonstrated positive results in a Phase 2b trial. All four dosing regimens achieved significantly greater weight reduction from randomization to Week 28 compared with placebo (P<0.001). Notably, after transitioning to monthly dosing, weight-loss effects remained strong and sustained, with no plateau observed by Week 28, suggesting the therapy may support a once-monthly dosing regimen. Multiple Phase 3 trials of PF'3944 are currently underway.Additionally, Viking Therapeutics’ dual GIP/GLP-1 receptor agonist VK2735 reported Phase 2 results published in Obesity, while enrollment for its Phase 3 trial was completed this quarter. Altimmune’s candidate pemvidutide received FDA Breakthrough Therapy designation earlier this year for the treatment of MASH, and the company has reached agreement with the FDA on the key design of its Phase 3 registrational trial targeting patients with moderate-to-severe liver fibrosis.Meanwhile, Novo Nordisk reported that its fixed-dose combination therapy CagriSema outperformed semaglutide in Phase 3 trials in both weight reduction and HbA1c improvement. CagriSema combines the long-acting amylin analog cagrilintide (2.4 mg) with semaglutide (2.4 mg). Zealand Pharma and AbbVie also reported encouraging results this quarter for amylin-targeting therapies petrelintide and ABBV-295, with positive Phase 2 and Phase 1 results, respectively, for the treatment of obesity.Importantly, the application of GLP-1 therapies is expanding beyond metabolic diseases. This quarter, Eli Lilly reported that its GLP-1/GIP dual receptor agonist Zepbound (tirzepatide) combined with the IL-17A monoclonal antibody Taltz (ixekizumab) met primary endpoints in two Phase 3 trials targeting overweight or obese patients with moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). These findings suggest that GLP-1 therapies may form new combination treatment strategies alongside psoriasis biologics.Beyond GLP-1–related therapies, several peptide drugs also advanced in other disease areas. For example, PRI-002, an oral peptide therapy from Priavoid targeting β-amyloid (Aβ) oligomers, demonstrated amyloid-related imaging abnormality (ARIA) rates comparable to the placebo group in previous Phase 3 studies.In addition, results from a Phase 1/2 study showed that a patient with both familial adenomatous polyposis (FAP) and associated desmoid tumors experienced significant improvement after 60 weeks of treatment with zolucatetide, a potential first-in-class peptide therapy developed by Parabilis Medicines. Compared with baseline, both the number and size of duodenal polyps were significantly reduced, with disease stage improving from Spigelman stage II to stage I, while the desmoid tumor diameter decreased by 52.2%. According to the company, zolucatetide is the first inhibitor designed to directly block the interaction between β-catenin and TCF.Partnerships and FinancingOn the industry collaboration front, several large pharmaceutical companies announced peptide-focused partnerships this quarter. In January, AstraZeneca and CSPC Pharmaceutical Group announced a strategic collaboration worth up to $3.5 billion to advance eight next-generation therapies targeting obesity and type 2 diabetes. The partners will initially advance four programs combining CSPC’s AI-driven peptide discovery platform with its proprietary LiquidGel once-monthly delivery technology. In February, Novartis entered into a collaboration with Unnatural Products (UNP) worth more than $1.7 billion to develop macrocyclic peptide therapeutics.In terms of financing, several emerging companies also secured strong investor support. Parabilis Medicines completed a Series F financing exceeding $300 million earlier this year to advance the development of zolucatetide. Meanwhile, Pinnacle Medicines completed $89 million Series B financing in March to accelerate the clinical development of its pipelines.WuXi AppTec Supports Innovation in Peptide TherapeuticsAs peptide therapeutics continue to expand into obesity, metabolic diseases, and a growing range of innovative indications, molecular designs are becoming increasingly sophisticated. From fatty-acid modification and PEGylation to protein fusion and peptide conjugation, many next-generation peptide drugs are engineered to achieve longer half-lives and improved therapeutic performance. However, these innovations also introduce new analytical challenges in drug development. Particularly during clinical studies, accurately characterizing the in vivo exposure profile and immunogenicity risks of peptide drugs, and understanding how structural modifications may influence these parameters, has become critical for advancing therapies into later-stage development.Against this backdrop, integrated bioanalytical capabilities supporting both pharmacokinetics (PK) and immunogenicity assessment are becoming increasingly essential. To help partners address these challenges, WuXi AppTec Bioanalytical Services (BAS), supported by a highly mature bioanalytical technology platform, has established a systematic analytical solution tailored to the development needs of next-generation peptide therapeutics. This integrated platform effectively addresses the complex challenges associated with pharmacokinetics (PK) and immunogenicity studies in clinical trials. As peptide drugs continue to increase in molecular weight, incorporate more structural modifications, and adopt increasingly complex conjugation formats, their bioanalysis presents a series of unique challenges.In LC–MS/MS analysis, peptides often exhibit broad charge state distributions and heterogeneous ionization efficiency, leading to signal dispersion and ion suppression that can compromise sensitivity and method robustness. Meanwhile, peptides typically possess limited epitopes and high homology to endogenous counterparts, resulting in low immunogenicity and challenges in generating highly specific antibodies, as well as increased susceptibility to endogenous interference and cross-reactivity in ligand-binding assays (LBA). In addition, structural modifications such as fatty acid conjugation, PEGylation, or protein fusion—while extending half-life—may introduce additional immunogenicity risks (e.g., anti-PEG antibodies), further complicating anti-drug antibody (ADA) and neutralizing antibody (NAb) assessments.To address these challenges, WuXi AppTec BAS integrates high-sensitivity LC–MS/MS, immunocapture–mass spectrometry, ELISA/MSD platforms, and cell-based functional assays to enable seamless support from PK analysis to comprehensive immunogenicity evaluation. Through optimized sample preparation strategies, implementation of immunocapture techniques, and adoption of bottom-up approaches such as trypsin digestion, the platform significantly enhances detection sensitivity and reduces matrix interference, ensuring robust and specific analysis of structurally complex and long-chain peptides. For immunogenicity assessment, a tiered evaluation framework is established, incorporating bridging ADA assays, confirmatory testing, and titer determination, alongside advanced strategies such as acid dissociation (ACE) and minimum required dilution (MRD) optimization to improve drug tolerance and assay sensitivity. In parallel, careful optimization of labeled reagents and assay conditions minimizes endogenous interference and non-specific binding, while cell-based NAb assays provide functional evaluation of neutralizing responses—enabling an end-to-end immunogenicity assessment workflow for complex peptide and peptide-conjugated therapeutics.WuXi AppTec BAS has successfully supported clinical PK and immunogenicity studies for a wide range of peptide therapeutics, including GLP-1 analogs and insulin analogs, delivering end-to-end capabilities from method development and validation to sample analysis. Enabled by standardized workflows and integrated multi-technology expertise, WuXi AppTec provides high-sensitivity, high-reliability bioanalytical support for peptide therapeutics, accelerating the advancement of innovative peptide drugs from research into clinical development.参考资料：[1] 各公司官网免责声明：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

加速审批临床研究

100 项与 PRI-002 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
阿尔茨海默症	临床2期	捷克	Priavoid GmbH	2024-02-15
阿尔茨海默症	临床2期	德国	Priavoid GmbH	2024-02-15
阿尔茨海默症	临床2期	意大利	Priavoid GmbH	2024-02-15
阿尔茨海默症	临床2期	荷兰	Priavoid GmbH	2024-02-15
阿尔茨海默症	临床2期	波兰	Priavoid GmbH	2024-02-15
阿尔茨海默症	临床2期	西班牙	Priavoid GmbH	2024-02-15
轻度认知障碍	临床2期	捷克	Priavoid GmbH	2024-02-15
轻度认知障碍	临床2期	德国	Priavoid GmbH	2024-02-15
轻度认知障碍	临床2期	意大利	Priavoid GmbH	2024-02-15
轻度认知障碍	临床2期	荷兰	Priavoid GmbH	2024-02-15

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06182085 (PRImus‑AD, Pubmed \| Alzheimers Dement)	临床2期	-	300	PRI-002 300 mg	簾齋蓋窪鹽蓋獵鏇顧獵(廠艱餘範網觸築鬱鬱鹽) = 願願壓廠壓積製窪襯衊簾繭築選顧餘構觸餘醖 (壓夢範淵範選觸選窪觸 )	积极	2025-12-01
				PRI-002 600 mg	築願顧憲淵壓積壓艱夢(積築廠艱醖鏇餘蓋鬱選) = 蓋範壓蓋積積艱簾遞遞構鬱憲衊襯積網憲鬱襯 (窪衊鬱簾積願夢餘獵窪 ) 更多
CTAD2022	临床1期	Aβ1-42 \| Aβ oligomers	20	RD2	衊製齋糧鬱積糧觸齋觸(鹹鑰顧蓋積製範顧觸願) = 13 patients reported in total 27 adverse events while no serious adverse event was noted. There was no statistical difference regarding adverse events between treatment and placebo. In contrast to reported anti- Aβ-antibody-treatments, no ARIA events have been observed. 夢膚鹽獵衊齋醖憲遞齋 (選醖網憲願艱醖鹹積淵 ) 更多	积极	2022-12-03
				Placebo
NCT04711486 (AAIC 12022 \| AAIC 22022) 人工标引	临床1期	阿尔茨海默症	19	PRI-002 300 mg	願獵醖襯選衊衊鑰築繭(淵襯簾廠選憲衊網築築) = 蓋餘窪築範選鑰廠積醖範遞廠夢範構餘願艱積 (願鏇廠窪窪觸衊鑰齋構 ) 更多	积极	2022-08-01
				Placebo	-