Topical histone deacetylase inhibitor remetinostat improves IMQ-induced psoriatic dermatitis via suppressing dendritic cell maturation and keratinocyte differentiation and inflammation

Article

作者: Jiang, Qian ; Zhou, Xingchen ; Huang, Huining ; Jin, Liping

Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes and infiltration of immune cells. Although psoriasis has entered the era of biological treatment, there is still a need to explore more effective therapeutic targets and drugs due to the presence of resistance and adverse reactions to biologics. Remetinostat, an HDAC inhibitor, can maintain its potency within the skin with minimal systemic effects, making it a promising topical medication for treating psoriasis. But its effectiveness in treating psoriasis has not been evaluated. In this study, the topical application of remetinostat significantly improved psoriasiform inflammation in an imiquimod-induced mice model by inhibiting CD86 expression of CD11C⁺I-A/I-E⁺ dendritic cells (DCs) in the skin. Moreover, remetinostat could dampen the maturation and activation of bone marrow-derived DCs in vitro, as well as the expression of psoriasis-related inflammatory mediators by keratinocytes. In addition, remetinostat could promote keratinocyte differentiation without affecting its proliferation. Our findings demonstrate that remetinostat improves psoriasis by inhibiting the maturation and activation of DCs and the differentiation and inflammation of keratinocytes, which may facilitate the potential application of remetinostat in anti-psoriasis therapy.

2024-10-01·ARCHIV DER PHARMAZIE

Soft drug inhibitors for the epigenetic targets lysine‐specific demethylase 1 and histone deacetylases

Article

作者: Baniahmad, Adina A. ; Seitz, Johannes ; Schüle, Roland ; Auth, Marina ; Preissl, Sebastian ; Hein, Lutz ; Schulz‐Fincke, Johannes ; Prinz, Tony ; Jung, Manfred ; Tzortzoglou, Pavlos ; Willmann, Dominica ; Hau, Mirjam ; Schmidtkunz, Karin ; Metzger, Eric

Abstract:

Epigenetic modulators such as lysine‐specific demethylase 1 (LSD1) and histone deacetylases (HDACs) are drug targets for cancer, neuropsychiatric disease, or inflammation, but inhibitors of these enzymes exhibit considerable side effects. For a potential local treatment with reduced systemic toxicity, we present here soft drug candidates as new LSD1 and HDAC inhibitors. A soft drug is a compound that is degraded in vivo to less active metabolites after having achieved its therapeutic function. This has been successfully applied for corticosteroids in the clinic, but soft drugs targeting epigenetic enzymes are scarce, with the HDAC inhibitor remetinostat being the only example. We have developed new methyl ester‐containing inhibitors targeting LSD1 or HDACs and compared the biological activities of these to their respective carboxylic acid cleavage products. In vitro activity assays, cellular experiments, and a stability assay identified potent HDAC and LSD1 soft drug candidates that are superior to their corresponding carboxylic acids in cellular models.

2023-06-01·Journal of labelled compounds & radiopharmaceuticals

Nitrilase mediated mild hydrolysis of a carbon‐14 nitrile for the radiosynthesis of 4‐(7‐hydroxycarbamoyl‐[1‐¹⁴C‐heptanoyl]‐oxy)‐benzoic acid methyl ester, [¹⁴C]‐SHP‐141: A novel class I/II histone deacetylase (HDAC) inhibitor

Article

作者: Moody, Thomas S. ; Chappell, Todd ; Kitson, Sean L. ; Watters, William ; Mazitschek, Ralph

A strategy has been developed for the carbon‐14 radiosynthesis of [14C]‐SHP‐141, a 4‐(7‐hydroxycarbamoyl‐heptanoyloxy)‐benzoic acid methyl ester derivative containing a terminal hydroxamic acid. The synthesis involved four radiochemical transformations. The key step in the radiosynthesis was the conversion of the 7‐[14C]‐cyano‐heptanoic acid benzyloxyamide [14C]‐4 directly into the carboxylic acid derivative, 7‐benzyloxycarbamoyl‐[14C]‐heptanoic acid [14C]‐8 using nitrilase‐113 biocatalyst. The final step involved deprotection of the benzyloxy group using catalytic hydrogenation to facilitate the release of the hydroxamic acid without cleaving the phenoxy ester. [14C]‐SHP‐141 was isolated with a radiochemical purity of 90% and a specific activity of 190 μCi/mg from four radiochemical steps starting from potassium [14C]‐cyanide in a radiochemical yield of 45%.

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项与 Remetinostat 相关的新闻（医药）

2026-01-15

·漫步羊

错位竞争下的破局思路：渐冻症药物开发的潜在路径分析

缘起最近这种令人感到有些压抑且排他、经费紧缩而内卷的学术环境，让我萌生了创业或者转行投资的想法。在研读芒格老头子的教诲时，他的错位竞争策略给了我很大启发: 要去到那些大象去不到的地方，如果现有的规则对你不利，就不要在规则里证明自己。我是一个生物技术爱好者，在过去的十一年里，从HIV治愈研究到基因治疗，再到蛋白设计和抗体工程、AAV进化，我感觉自己做了海量的实验。虽然非常努力且享受这个过程，但不得不承认成果寥寥。回顾以往，我最大的收获是发现自己并没有聚焦于关键的科学问题。所在问题的价值直接决定了成果的分量，商业竞争和药物研发亦是如此。将现在的单抗、双抗、ADC、siRNA等平台技术应用于高度内卷的肿瘤、自免代谢领域，已经是大药企和资深创业者的游戏。我想对于初创者来说，将基因治疗用于介于罕见病和常见病之间的疾病，可能具备更好的错位竞争优势。并且对于显著未满足的临床需求，临床入组速度快，患者支付意愿强，监管机构提供的FTD、BTD以及ODD等注册路径对创业者会更加有利。这样可以让个人创造力去对冲更高的药物研发风险，同时降低现实世界中的资源阻力。于是我问 Gemini，如果从基因治疗的角度看，哪些疾病或靶点的竞争格局较好且有巨大的潜在市场？总体上它的看法和我相似，但是排在第一的神经退行性疾病，包括帕金森病（PD）和肌萎缩侧索硬化症（Amyotrophic Lateral Sclerosis, ALS），却有点让我意外。全球 PD 患者超过 1000 万，目前缺乏有效延缓疾病的药物，患者极度痛苦且严重影响生活质量，潜在市场在数千亿美元，市场格局可以说是完美的。但其发病机理不清晰且缺乏潜在有效靶点，从药物开发的角度看，这已经超出了目前的技术范畴。随后我查阅了 ALS 的资料，不查不知道，一查吓一跳，原来 ALS 就是我们常说的渐冻症。。 ALS 全球约有四五十万人，每年新发 12 到 14 万人。其中中国有 6 到 8 万人，新发约 2 到 2.5 万人/年；欧美有 8 到 10 万人，新发约 3 到 3.5 万人/年。ALS 诊断后平均寿命仅 2 到 5 年，存在显著的未满足临床需求。当前市场规模在 10 亿美金左右，但显然潜在市场是跟疗效挂钩的，预计在 200 亿美金左右。虽然 ALS 的致病机理还不是非常明确，但似乎存在一些疾病表型和分子机理上的共性，这给药物开发留下了一些落脚点。下面我来讲讲 ALS 的致病机理、研发现状以及潜在的开发路径。渐冻症致病机理 ALS 是一种罕见的进行性神经退行性疾病，主要影响运动神经元（Motor Neuron, MN）。患者会面临肌肉逐渐萎缩和无力以至瘫痪，似乎身体被逐渐冻住一般。从无法行走到无法说话、吞咽、呼吸，最终导致呼吸衰竭和死亡。其最显著的特征是上运动神经元（Upper Motor Neuron, UMN）和下运动神经元（Lower Motor Neuron, LMN）的退化和死亡。UMN 连接大脑和脊髓，LMN 则连接脊柱中的 UMN 和身体的肌肉。运动神经元是负责随意肌收缩的细胞，主要参与运动及吞咽、发声、呼吸等重要生理功能。二者的退化意味着所支配肌肉的进行性瘫痪。由于 MN 的进行性变性导致信号发送停滞，大脑丧失了启动和控制肌肉运动的能力，最终当肺部横膈膜肌萎缩瘫痪时，患者会因呼吸衰竭死亡。约 10% 的 ALS 患者是家族性遗传原因，迄今为止发现的突变约占家族性病例的70%，其他患病原因则尚不明确。目前大多理论集中在基因和环境因素的复杂相互作用方面。涉及的 4 个主要基因包括 SOD1、TARDPB、FUS、C9orf72，以及约 15 个次要基因，如 ALS2、SETX、VAPB、FIG4、ERBB4、MATR3、ANG、OPTN、VCP、UBQLN2、CHMP2B、PFN1、hNRPA1 A2/B1、TUBA4A、NEK1。图1. 渐冻症的发病机制及相关基因 (Péladeau, C. et al. (2021) Int J Mol Sci.; Morgan,S.et al. (2016) British MedicalBulletin) 尽管家族性ALS 的遗传原因存在巨大的异质性，但家族性和散发性 ALS 在其病理和临床特征上具有相似性，这提示导致 MN 变性的细胞和分子机制是相似的。通过研究病人的基因变化，大部分科学家认为 ALS 可能与轴突结构和动力学、细胞凋亡和坏死、线粒体功能障碍、谷氨酸兴奋毒性、炎症以及氧化应激有关。患者会表现出神经病理变化，如近端轴突神经丝状肿胀，神经丝（Neurofilament, NF）和外周蛋白在轴突和神经元胞体中聚集。此外还包括具有磷酸化 NF 和泛素免疫反应性的核周包涵体。在一些家族性病例中，还存在 Cu/Zn 超氧化物歧化酶免疫反应性、路易小体样胞质神经元包涵体、高尔基体断裂、远端轴突口径减少、轴突华勒变性以及树突衰减等神经病理性改变。从碎片拼图到药物研发思路上面的病理过程其实十分的笼统和抽象，容易让人无从下手。要找药物靶点，先要理解潜在的分子病理机理。下面我们就把一个一个的知识碎片拼凑起来，得到一个关于ALS的潜在分子机理，基于这个理解去选择靶点，开发药物。首先，TDP-43异常聚集出现在几乎所有的 ALS 和约一半的额颞叶变性（FTLD）患者中。它还涉及边缘系统相关年龄依赖性 TDP-43 脑病（LATE）、阿尔茨海默症（AD）、慢性创伤性脑病（CTE）、亨廷顿舞蹈症（HD）等。说明TDP-43异常聚集跟一些共同的细胞机制有关。 TDP-43存在一个 mRNA-TDP-43 自反馈调控系统。TDP-43 的mRNA可以结合 TDP-43 蛋白，诱导自身mRNA 的降解。当细胞核感知 TDP-43 不足时，TDP-43的抑制解除，会大幅提高mRNA 的出核比例从而提高TDP-43蛋白的表达。 TDP-43 异常聚集存在4种折叠构象，ALS中主要为fold-B。聚集主要由 C 端低复杂性结构域（Low Complexity Domain, LCD）中间的疏水 β 折叠驱动。TDP-43 聚集体的不同折叠方式与大脑位置和疾病高度相关。目前已知有 24 个疾病相关突变聚集于 TDP-43 纤维折叠区，说明 TDP-43 的异常折叠是 ALS 和 FTLD 的直接原因。 TDP-43 纤维化聚集体存在在脑组织裂解上清或沉淀中，沉淀中主要是 P280 酶切后的产物。Kumar 等人在 2023 年发表于《Nature Neuroscience》的研究指出，TDP-43 的酶切和淀粉样核心暴露是其病理传播所必需的。最近发现环境应激或衰老会诱发 LCD 区域的异常翻译后修饰，如磷酸化和乙酰化，导致了同样的聚集结果。说明TDP-43 磷酸化和乙酰化修饰和蛋白酶切产生了高毒性的LCD蛋白聚集种子。一个有意思的问题就是ALS 为什么会造成 MN 凋亡而不是其他神经元？因为 MN 代谢活跃且体积大，从大脑到肌肉就连接了两个神经元，UMN 直径可达 60 微米，需更高效地清除错误折叠蛋白，但自噬系统超负荷易引发损伤。那神经元代谢跟蛋白异常折叠有什么直接关系呢？多种病理过程会导致TDP-43 的异常折叠，比如分子伴侣蛋白活性不足、核转运障碍导致的转录谱紊乱、下游代谢紊乱以及蛋白降解系统失衡。当细胞面临这些压力时会形成应激颗粒（Stress Granule, SG）用于保护 RNA。正常情况下压力消失后 SG 会解散，TDP-43 回到细胞核。但在慢性压力或基因突变存在时，这种可逆过程会失控。TDP-43 会在 SG 中发生相变，即液-液相分离，逐渐变为不可溶的固体聚集体。胞质中的 TDP-43 聚集物具有类似朊病毒的性质，能诱导健康的蛋白也发生错误折叠。这会导致细胞核内该蛋白枯竭，进而引发关键 RNA 的错误剪接，如 STMN2 和UNC13A 的隐性外显子保留，直接破坏神经元完整性。 MN 对这种应激更敏感。体外实验证实，多种应激源如氧化应激、内质网应激等可诱导神经元过度应激，导致 TDP-43 从细胞核移位至细胞质并形成聚集体。这种异常聚集似乎存在一个耐受区间。ALS患者大脑H&E 染色结果显示，MN 的TDP-43 纤维聚集体展现出明显的“有或无”两种状态，这是典型的酶促反应表现，说明纤维聚集体会在某些诱因触发下发生指数级增长。图2. ALS前额叶皮层进行 TDP-43 抗体免疫组织（棕色）染色 (Diana A. et al., Nature 2021) 从蛋白折叠角度看，TDP-43 在正常生理条件下不会自发折叠，这是进化下的必然结果。而ALS中TDP-43的异常聚集说明TDP-43疏水 β 折叠核心的形成可能是在SG局部高浓度或其他辅助分子如 RNA 的作用下形成的。最后，从基因-表型分析也可知，疾病相关突变基因C9ORF72、SOD1、TARDBP 等参与 RNA 代谢、细胞运输、自噬与降解等共同机制，最终都会出现不可逆的 TDP-43 毒性聚集体。这说明TDP-43纤维化聚集的形成存在“RNA 加工异常/代谢异常-细胞应激-TDP-43 纤维化聚集-运动神经元凋亡”这一隐含通路。图3. 推测的TDP-43纤维形成机理 (Senthil T. K. et al., Nature Neuroscience 2023) 渐冻症临床研究现状渐冻症已被发现 200 多年，但疗法和突破非常有限。近 30 年来，利鲁唑（Riluzole）、依达拉奉（Edaravone）、Relyvrio 以及托夫生（Tofersen）等药物逐步面世。尤其 Tofersen 获批用于治疗具有 SOD1 突变的患者，成为美国FDA批准的首款治疗遗传性 ALS 的ASO疗法，也是首款基于生物标志物加速批准的 ALS 疗法。当下有近百款新药处于临床研究阶段，涵盖小分子、寡核苷酸、多肽、细胞和基因治疗药物等。目前探索的策略包括调节兴奋性、提供神经保护、抑制氧化应激、调节代谢以及降低致病基因表达等。说实话，目前并没有看到特别明显的疗效，现有疗法依然无法完全阻止或逆转病变。例如，尽管有数款药物获批，其疗效多基于生物标志物上的改善。例如 Ionis 获批的 SOD1 ASO 疗法可降低CSF中 60% 的神经丝轻链（Neurofilament Light chain, NfL），但在 28 周时未能显著改善 ALS 功能评分量表修订版（ALSFRS-R）。尽管功能改善不明显，NfL 的显著下降至少说明下调聚集体可以降低神经元炎症和凋亡。同时，两个完全获批的药物 Riluzole 和 Edaravone 分别抗谷氨酸能过度激活和抗氧化应激，说明 MN 的应激反应是重要病理因素。此外，Neuvivo 开发的巨噬细胞炎症调节剂 NP001 在高 CRP 患者中有效，说明自免炎症反应也参与了ALS的进展。就在近日，VectorY Therapeutics 一款 AAV-scFv（单链抗体）抗体疗法 VTx-002 获得 FDA 的FTD 资格，用于推进启动一项 PIONEER-ALS 1/2 期临床试验（NCT07287397），旨在治疗 TDP-43 病理改变的 ALS。由于这种病理改变覆盖了约 97% 的患者，其意义重大。图4. VTx-002的作用原理 (ALS/MND poster) 其使用的 AAV5.2 载体是引进自 Shape Therapeutics 的深脑穿透型 AAV。这个单链抗体可以精准识别并清除细胞质中的错误折叠的 TDP-43 聚集物，并有望恢复 TDP-43 在细胞核的正常生理功能。有意思的是，结合 TDP-43 不同位点的 scFv 可以恢复大部分 TDP-43 M337V 突变引起的 RNA 错误剪切，且靶向 C 末端的scFv 几乎不改变 RNA 的剪切模式。同时scFv 完全预防了 M337V 突变神经元在压力应激后的纤维化聚集，并恢复了下游基因表达。这个数据从细胞水平上证明了通过操控 TDP-43 来调控纤维化聚集的可能性。图4. VTx-002可清除M337V突变神经元的TDP-43纤维聚合物 (ALS/MND poster) 最后，Immunity Pharma 的 IPL344 治疗 ALS 的 2a 期试验显示，与历史数据相比，其 ALSFRS-R 进展速度减缓了约 60%。IPL344 是一种生物活性肽，能直接激活受损的 Akt 通路。但需要注意，这里的对照是历史对照，数据说服力相对有限。 ALS 治疗的潜在开发路径从上面分析可知，ALS 致病原因多样，但总体遵循“RNA 加工/代谢异常-细胞应激-应激颗粒形成-TDP-43 纤维化聚集-运动神经元凋亡”这一隐含通路。从药物开发角度看，最好能找到通用的靶点或机制，尽量覆盖最多人群的同时获得疗效。因此，SG 形成和 TDP-43 纤维化聚集是理想的靶点。由于 TDP-43 在mRNA加工中的核心作用，我们需要干预纤维化聚集过程的同时维持其功能。有多个潜在路径去实现这个目标。第一条路是开发工程化的TDP-43*。它可以替换原来的 TDP-43 履行生理功能，但自身又不会产生应激后的纤维化聚集。这样高表达的工程化 TDP-43* 不仅可以完成功能替换，还能通过自反馈机制降解人类自身的TDP-43 mRNA，从而终止纤维化聚集的恶性循环。我们或许可以从长寿物种中寻找抗纤维化 TDP-43* 序列，或者直接对 TDP-43 的疏水核心进行蛋白设计，破坏纤维聚集的疏水界面。幸运的是TDP-43在功能是非常保守的，序列差异主要发生在LCD区，且哺乳动物细胞互相替换TDP-4后仍能准确完成大部分RNA剪切和调控。如我所想，作为长寿且体型巨大的鲸鱼，其 TDP-43 的LCD展现出了极佳的抗聚合能力。第二条路是借鉴 VectorY 的思路去设计抗 TDP-43 纤维化分子，但VectorY的策略会干扰TDP-43的功能。因为TDP-43 纤维会在两端不断延伸，我们或许可以在纤维两端的结合面设计 Binder。这有点像人体内 DARPin（Designed Ankyrin Repeat Protein）蛋白两端的帽子样结构，用于中断纤维化的多米诺组装过程。可封闭纤维末端的Binder 理论上可以阻断纤维聚集，且不会像抗体那样产生对 RNA 剪切的干扰。图5. TLR分子β折叠重复单元以及两端帽状结构 (Christmas, P. 2010 Nature Education) 图6. TDP-43 fold-B纤维核心和疏水界面 (Senthil T. K. et al., Nature Neuroscience 2023) 最后一种思路是借鉴其他物种的纤维裂解系统，比如酵母或微生物中的 Hsp104强效解聚酶。宾大的James Shorter 团队在这个方向已经做了很多年的工作。这种六聚体环状解聚酶在低等真核生物中存在更强力的活性。但该策略存在几个挑战，首先ALS本身就是上游的代谢失调，提供额外的解聚酶大概率也解决不了系统代谢、供能等的问题。事实上临床上已经尝试过稳定HSP蛋白或提供营养因子治疗ALS，但效果一般。其次，动物进化出了更高级的泛素降解系统，Hsp104 需要与酵母Hsp70 和Hsp40 系统协作来区分底物特异性。在人体内缺乏这种区分系统，因此不可避免地会遇到降解特异性和毒性的问题，成药概率较低。综上所述，我觉得干扰 TDP-43纤维化聚集过程是更现实的路径。结合聚集干扰分子和 AAV 载体，可实现在长时间的抗聚集保护和抗凋亡。目前这个方向探索者极少，非常值得一试。附表. 临床阶段ALS管线汇总

siRNA基因疗法

2026-01-15

·海南国卫生物

细胞科普｜《自然・医学》发布2026医疗风向标：11项试验将重塑医学，细胞治疗备受关注

最近，国际顶级医学期刊《自然・医学》（Nature Medicine）发布了一篇重磅年终盘点报告 ——《Eleven clinical trials that will shape medicine in 2026》。多位顶尖科研人员评选出他们心目中2026年“最具影响力的临床试验项目”，评选出11项临床试验。这些试验覆盖了广泛的研发领域，从基因疗法到前沿癌症治疗。 Nature Medicine 2026年最值得关注的11项临床研究 01 更持久的结核病疫苗（M72/AS01E）一项III期临床试验，评估新型结核病疫苗在不同人群中的保护效果，旨在解决现有BCG疫苗在青少年和成人中保护力不足的问题。 02 长效中和抗体用于HIV治疗中断后的病毒控制通过长效广谱中和抗体，探索在停止常规抗逆转录病毒治疗后维持病毒抑制的可能性。 03 长新冠的药物治疗探索一项开放标签、平台型随机临床试验，评估多种抗炎及抗凝药物在缓解长新冠症状中的潜在作用。 04 双重拉沙热–狂犬病疫苗一种基于灭活狂犬病病毒载体的疫苗，探索同时预防拉沙热和狂犬病的可行性。 05 靶向IL-6的心血管炎症治疗通过抑制IL-6通路，评估其在动脉粥样硬化及慢性肾病相关心血管事件中的干预效果。 06 泛RAS抑制剂治疗转移性胰腺癌比较新型口服RAS抑制剂与标准化疗在转移性胰腺癌中的疗效与安全性。 07 mRNA CAR-T细胞治疗重症肌无力利用mRNA技术进行短暂表达的CAR-T细胞治疗，探索其在自身免疫性神经肌肉疾病中的应用。 08 慢性肉芽肿病（CGD）的基因编辑干细胞治疗采用患者自身造血干细胞，经基因编辑后回输，评估其在CGD中恢复中性粒细胞功能的效果。 09 细胞免疫治疗用于转移性乳腺癌将细胞免疫治疗与免疫检查点抑制剂联合，用于既往多线治疗失败的转移性乳腺癌患者。 10 自体骨髓来源干细胞治疗神经系统疾病通过静脉和鼻腔途径给药，探索干细胞改善多种神经系统疾病功能的可能性。 11 靶向Lp(a)的反义寡核苷酸治疗心血管疾病评估降低脂蛋白(a)是否能够转化为心血管事件风险的实际下降。值得关注的是，这些试验不再局限于“传统药物研发”，而是大量融入了细胞治疗、基因编辑、长效抗体等前沿技术。其中，细胞治疗及相关技术更是成为“破局关键”，它们不再满足于缓解症状，而是试图从“细胞层面修复损伤”“调控免疫反应”“修正基因缺陷”，为过去无药可治的疾病提供“根治性”方法。 1.聚焦干细胞修复大脑（NEST 试验）干细胞修复大脑（NEST 试验）中风、帕金森病、渐冻症（ALS）、阿尔茨海默病，这些神经系统疾病的共同难题是“大脑损伤不可逆”。传统治疗只能缓解症状，却无法修复已经坏死的神经细胞，患者往往会逐渐失去运动、语言甚至认知能力。 NEST试验则提出了一个新的解决方案：从患者骨髓提取干细胞，通过静脉/鼻腔喷雾无创输送至大脑损伤区域，改善各类神经疾病，已治疗200人，部分患者数周内显效，2026年公布长期随访数据。这项试验的灵感源于 2010 年的一次“意外发现”，当时医生为眼病患者进行视网膜干细胞手术时，竟发现患者的运动障碍、语言迟缓等神经系统症状也明显改善。基于这一发现，研究团队提出：从患者自身骨髓中提取干细胞，通过“静脉注射”或“鼻腔喷雾”的方式送回体内，让干细胞自行“归巢”到大脑损伤区域，修复受损神经。与传统干细胞治疗需要开颅手术等方法不同，鼻腔喷雾的方式是无创的，患者易于接受。按照试验计划，2026年将公布更多长期随访数据。如证实安全有效，这种“无创干细胞疗法”将改变神经系统疾病的治疗模式。 2.鼻滴干细胞改善脑损伤的临床研究案例（1）鼻滴干细胞干预脑损伤：抑制炎症，缩小损伤最新发表在《Annals of Neurology》上的研究，带来了一项新的解决方案：研究者进行动物实验创新性地将脐带来源的间充质干细胞通过鼻腔给药，送达受伤的大脑。结果显示，这种方法不仅单独使用时效果显著，更能与低温疗法强强联合，产生 1+1>2 的协同效应。（2）干细胞治疗缺血性脑损伤：心脏骤停后早期经鼻给药全脑缺血性脑损伤是心脏骤停患者复苏后死亡和长期残疾的主要原因。低温和神经保护剂是部分改善复苏后神经功能预后的两种策略。然而，这些治疗方法的治疗效果的报道并不一致。干细胞疗法由于其增殖和分化为功能性神经细胞的潜力，已成为一种有前途的保护策略。该研究回顾了通过鼻内途径进行干细胞治疗在灵长类动物和临床研究中的现状，以及干细胞治疗心脏骤停后缺血性脑损伤的治疗窗口，为干细胞治疗由心脏骤停引起的全脑缺血损伤提供了新的见解。（3）意大利研究人员证实：鼻腔滴入干细胞改善神经系统疾病具有抗炎功效 2020年6月4日，在《干细胞转化医学》国际期刊杂志中，意大利Silvia Coco博士在一次鼻腔滴入干细胞治疗神经系统疾病的研究中表示：“通过非侵入性途径应用，让MSC-EVs（干细胞分泌的一种物质）的输送有效证明了其抗炎功效，让MSC-EVs更快发挥作用治疗阿尔茨海默病。” 写在最后《Nature Medicine》的文章不仅是“预测未来”，更是在“揭示现实”：细胞治疗改变医学边界的进程，早已在全球专家的共识中加速推进。 2026年，那些即将报告的临床试验数据、落地的行业规范、惠及患者的治疗方案，都将证明：生物学家乔治·戴利的预言正在走向现实——“21世纪属于细胞治疗”。参考资料： [1] May. (2025) Eleven clinical trials that will shape medicine in 2026. Nat Med., doi: 10.1038/s41591-025-04083-x. [2] De Theije CGM, De Palma ST, Vaes JEG, et al. Intranasal Wharton's Jelly-Derived Mesenchymal Stem Cell Therapy, Alone or in Conjunction With Therapeutic Hypothermia, Alleviates Neonatal Hypoxic-Ischemic Brain Injury in Mice. Ann Neurol. 2025;98(6):1380-1394. [3] 医学界. [4] Weber, R.Z., Achón Buil, B., Rentsch, N.H. et al. Neural xenografts contribute to long-term recovery in stroke via molecular graft-host crosstalk. Nat Commun 16, 8224 (2025). [5]Nabity TS, Ransom JT. Treatment of severe traumatic brain injury with human bone marrow mesenchymal stem cell extracellular vesicles: a case report. Brain Inj. 2025;39(4):330-335. - END- 本内容由海南国卫生物编辑整理部分图文素材源于网络，内容有改动版权归原作者所有，侵删！ CONTACT US 400-650-7895 -

细胞疗法基因疗法信使RNA疫苗免疫疗法

2026-01-14

·药明康德

致敬梦想 | 2026药明康德全球论坛图文速递 | Bilingual

世纪之交的2000年，人类首次触及生命蓝图的轮廓。那一刻，一个关于医学的梦想被点亮——更深入地理解疾病，更理性地设计药物，让改变命运的治疗，走向更多生命。也正是在这一年，药明康德诞生。与全球创新者同行，将梦想化为笃定的初心。 25年，梦想没有停留在想象中。它走进实验室，融入临床中，在一次次协作与托付里，缓慢生长，不断延展。站在2026年的起点，第14届药明康德全球论坛在旧金山如期举行。来自世界各地的追梦人再度相聚，以“B.O.L.D.”为名，回望走过的25年，也眺望仍在前方的梦想。向那些始终相信科学、坚持创新、并以行动推动医学向前的人——致敬。欢迎在欢迎致辞中，论坛主席、药明康德副总裁蔡辉博士邀请大家一起回望过去25年的来路。她说，每年1月的相聚，从来不只是一次会议，更像是一种约定：提醒我们生物医药产业之所以能够不断向前，是因为选择彼此信任、并肩同行。围绕论坛长期坚持的主题“B.O.L.D.”，蔡辉博士进一步分享了她的理解：BOLD，不只是打破边界、探索未知，更是在纷繁复杂的世界中保持清醒、稳稳走好每一步，并始终把患者放在心中最重要的位置。这是一条坚实而笃定的路，也是一段由无数双手共同托举、携手走向未来的同行之旅。时代创新脉动站在本世纪下一个25年的起点，我们不禁思考，这一路走来，产业取得了哪些令人瞩目的突破，又有哪些瓶颈仍待解决？在开场讨论中，多位行业领袖从创新突破转化、临床开发、监管与投资等多个维度切入，回顾过去，审视当下，共同探讨未来的发展方向。拜耳执行副总裁、制药业务BD&L负责人兼Leaps负责人Juergen Eckhardt博士回顾了过去25年间新治疗模式的涌现。他表示：“那是一个令人震撼的时期。在新治疗模式的开发，尤其是在将其真正带给患者方面，可能都是前所未有的。这些进展切实改变了许多患者的治疗范式。” 在肯定显著进步的同时，嘉宾们也对行业仍面临的深层挑战保持清醒认识。塔夫茨药物开发研究中心教授兼高级研究员Kenneth Kaitin博士指出：“药物研发的基本流程在过去60多年里几乎没有发生变化，这也由此带来了一系列新的挑战。” 在诸多挑战之中，如何提升临床试验效率成为多位嘉宾共同关注的焦点。MD安德森癌症中心高级副总裁兼首席科学官Giulio Draetta博士指出，与“患者不愿参与复杂临床试验”的传统认知不同，现实中患者往往展现出极大的慷慨与意愿，希望为早期研究提供支持。他认为，如果能够更好地衔接标准治疗与临床试验，在真实医疗场景中实现更高质量的执行，临床试验的参与度有望显著提升。从罕见病的视角出发，Parabilis Medicines董事长、总裁兼首席执行官Mathai Mammen博士补充道，企业需要更加系统地利用常规筛查数据，主动识别真正患病的潜在受试者。这一做法不仅有助于改善罕见病患者的诊断路径，也将为相关领域的临床试验推进带来实质性助力。在提升临床效率的技术路径中，人工智能（AI）被视为重要工具之一。Averin Capital联合创始人兼管理合伙人David Berry博士分享了AI在临床研究中的潜在应用前景。他指出，借助AI进行临床研究模拟，已发展到FDA允许开展“无需直接接触患者”的研究探索。尽管用AI模拟取代传统临床试验在过去被普遍视为不可能，但这一边界正在被不断推动。围绕“挑战不可能”这一话题，本场讨论主持人、RA Ventures风险合伙人Laura Shawver博士引用了一句她尤为认同的话：“困难的事情可以立刻去做，不可能的事情只是需要更长一点时间。”她表示，随着时间推移和能力积累，许多当下看似无法实现的目标，终将被逐一攻克。创新快车道在将科学真正转化为创新疗法、造福病患的进程中，哪些候选药物值得更进一步？我们又该如何做出抉择，让创新满足最迫切的医疗需求？在论坛的第二场专题讨论中，多家新锐公司的领军人物分享了加速新药研发的实践与策略，以及如何挑战传统研发路径，探索能够提升研发成功率的新技术、新模式与新理念。讨论伊始，专题讨论主持人、Forbion合伙人Jon Edwards博士抛出了一个基础却关键的问题：“我们所说的‘速度’究竟意味着什么？是充足的资金储备，还是经验丰富、少走弯路的团队？抑或是被寄予厚望、能够解决一切问题的AI？” 谈及AI在加速药物发现中的角色，Xaira Therapeutics首席医学官Paulo Fontoura博士表达了审慎而乐观的态度。他认为，AI的价值不仅在于提升速度，更在于帮助研发更快接近“真相”。“AI既能加深我们对生物学机制的理解，也能帮助我们将这些机制精准匹配到合适的患者身上，从而真正改善治疗结果。” 与此同时，多位嘉宾也提醒，在追求速度的过程中，科学判断与试验设计同样至关重要。Tenvie Therapeutics首席执行官兼总裁Tony Estrada博士指出，在中枢神经系统疾病领域，过快推进有时反而可能对靶点理解和生物学假设造成干扰，进而得出错误结论，延缓整个领域的发展。在讨论如何“更快做出更好的药”时，Dispatch Bio首席执行官Sabah Öney博士将焦点重新拉回患者本身。他强调，在实体瘤等疾病领域，患者所承受的时间压力极为真实。“如果我们哪怕晚了两年，意味着成千上万原本可能受益的患者，最终错失了机会。” Candid Therapeutics董事长、总裁兼首席执行官Ken Song博士则从研发决策的角度提出了一种更具挑战性的思维方式——通过设计“正确的实验”，尽早验证假设、快速作出取舍。他认为，能够尽早终止不可行项目，本身也是一种效率和责任的体现。细胞和基因疗法的时代承诺作为近年来迅速崛起的创新治疗模式之一，细胞和基因疗法已为治疗多种癌症和遗传病带来新的希望。2025年，Fred Ramsdell博士因在调节性T细胞领域的奠基性工作，荣获诺贝尔生理学或医学奖。与Sonoma Biotherapeutics创始人兼顾问Jeffrey Bluestone博士一道，他们回顾了细胞和基因疗法这一领域的发展历程与当前格局，并对未来的重点拓展方向做了展望。两位嘉宾重点探讨了调节性T细胞相关的基础研究如何为细胞疗法治疗自身免疫疾病奠定科学基础。Jeffrey Bluestone博士指出，诺奖研究揭示了免疫耐受并非免疫缺失，而是一个高度主动、由进化塑造的过程。调节性T细胞并非生物学的偶然产物，而是专门为维持自身组织稳态而进化出的关键细胞谱系。几乎所有自身免疫疾病以及移植排斥反应，都与这些细胞功能失调密切相关，这也为新一代治疗策略提供了清晰方向。 Fred Ramsdell博士则进一步阐述了调节性T细胞疗法相较于传统药物模式的独特优势。他表示，这一疗法的魅力在于充分利用了进化本身的智慧——这些细胞“知道该去哪里、该做什么”，能够主动维持组织健康。“让为保护组织而进化出的细胞，继续去完成它们本该承担的任务，本身就是一种极具潜力的治疗思路。” 以患者为先：我们肩负的方向无论科学怎么突破，技术怎么创新，目标最终都应回归到改善患者的生活。围绕中枢神经系统疾病、癌症、以及心血管疾病这三大“杀手”，三位长期奋战在临床与科研一线的科学家就各自擅长的领域展开深入交流，探讨哪些治疗与预防手段能够真正改变患者的生活，又有哪些更加患者导向的研发策略能真正推动创新惠及病患。专题讨论主持、Arena BioWorks董事长兼首席执行官Harvey Berger博士在开场时直言，在他看来，药物研发领域面临的根本问题仍是失败率过高。“如果失败率能够显著降低，速度本身就不会成为核心矛盾，患者所获得的改变将是深刻而持久的。” 对此，斯坦福心血管研究所主任、Greenstone Biosciences联合创始人Joseph Wu博士表达了审慎的乐观。他指出，随着技术手段的飞速发展，研究者如今能够在单细胞层面解析组织、基因与蛋白变化，并将这些发现迅速反馈至药物设计与功能验证之中。借助类器官等新模型，研发过程正逐步形成更高效的闭环。在肿瘤领域，帕克癌症免疫治疗研究所首席执行官Karen Knudsen博士强调，创新疗法已经开始在真实世界中产生深远影响。她指出，美国目前已首次在所有癌症总体层面实现五年生存率达到70%，这一历史性进展，正源于在多种难治性癌症中的持续治疗创新。谈及神经退行性疾病的未来，2025年科学突破奖（Breakthrough Prize）得主，加州大学旧金山分校Weill神经科学研究所主任Stephen Hauser博士同样持积极态度。他认为，随着生物标志物和通路研究的成熟，阿尔茨海默病、帕金森病、ALS等疾病的生物学复杂性正逐步被拆解。针对合理靶点、设计严谨的项目，有望在未来显著改善全球患者的生活质量。共创未来药明康德联席首席执行官陈民章博士首先向所有到场的演讲嘉宾、合作伙伴以及一路同行的朋友致以由衷的感谢。回望来路，他将时间拉回到2000年。那时的药明康德，只有四名员工、一间实验室，却已怀抱着一个朴素而坚定的信念：科学，能够改变生命。25年来，这份信念从未孤独前行。正是在全球创新生态圈的推动下，在一次次突破边界、一次次勇于承担风险的选择中，在顺境与逆境交织的旅程里，大家彼此扶持、共同坚守，走到了今天。围绕“共创未来”这一主题，陈民章博士强调，未来从来不是独自抵达的终点，而是在记忆中延续、在信任中生长、由选择携手同行的人们共同塑造。站在当下这个科学与技术持续突破的时代，这一共同的未来正逐渐具象化：全球范围内，已有超过50万项活跃的临床试验同步推进，每一项都承载着患者的希望。对药明康德而言，这个未来既承载理想，也扎根现实。它不仅由思想的交流所点亮，更由责任的担当、对协作的开放、在不确定中前行的勇气，以及作为一个共同体持续向前的承诺所铸就。而支撑这一切的核心始终清晰而坚定：将患者置于每一项决策的中心，持续践行那份不曾改变的信念——“让天下没有难做的药，难治的病”。健康老龄化的时代新篇老龄化不仅是全球社会面临的重要趋势，更是多种疾病的关键风险因素。“健康老龄化”究竟意味着什么？哪些突破有望改变衰老相关疾病的进程？针对这些问题，来自学术界、生物技术公司、大型医药企业与投资机构的专家齐聚一堂，探讨延长“健康寿命”（healthspan）的方法，并展望抗衰老领域正在加速到来的科学突破。 Hevolution基金会首席投资官William Greene博士指出了一个值得警醒的悖论：过去半个世纪中，人类寿命持续延长，但新增的寿命年限往往伴随着日益沉重的慢性疾病负担。他强调，未能真正“压低”与年龄相关疾病的发生曲线，是现代医学面临的最大未满足挑战之一。同时，他也将这一现实视为一次重要机遇——呼唤全新的医学路径，不仅要延长生命长度，更要提升生命质量。 XPRIZE基金会健康执行副总裁Jamie Justice博士从生物学角度切入，强调多种老龄相关疾病背后存在着共通的生物学基础。她认为，与其将这些疾病视为彼此孤立的状态，不如将“衰老本身”视为一个可干预的共同靶点。基于动物模型和转化研究的证据，她指出，科学界正逐步具备调控这一生物学过程的能力，从而有望同时影响多种疾病。她同时强调，XPRIZE正致力于推动这些科学洞见进入临床试验阶段，标志着老龄化研究正从理论走向现实验证。诺和诺德医学与转化科学高级副总裁兼首席医学官Filip Knop博士则将新兴的长寿科学与早已被反复验证的健康老龄化驱动因素联系起来。他指出，热量限制和身体活动在临床前研究、流行病学研究以及人群研究中始终表现出一致的积极作用。他进一步介绍，以司美格鲁肽为代表的疗法，可能正是通过作用于这些相同的生物通路，减少能量摄入、支持身体功能，从而带来广泛获益。更为重要的是，他强调，越来越多的证据表明，寿命与健康寿命之间的关系并非不可改变，这为有意义的医学干预提供了现实可能。巴克老龄化研究所首席执行官Eric Verdin博士阐述了健康老龄化领域的核心科学命题：许多慢性疾病共享由衰老驱动的共同机制。他以动物模型和百岁老人为例指出，这些机制是可以被调控的。尤其值得注意的是，百岁老人一生中真正受到与年龄相关疾病困扰的时间比例非常低。Verdin博士认为，这一鲜明对比为“压缩病程”（compressing morbidity）提供了有力证据——医学目标不应仅是延长寿命，更应是缩短患病时间，这在生物学上是可以实现的。 Retro Biosciences首席执行官Joe Betts-LaCroix先生则聚焦于那些已被证明能够显著改善健康寿命的干预手段。他强调，热量限制、GLP-1受体激动剂以及身体活动，是目前识别出的最具影响力的几大杠杆。其中，运动可能是一种被严重低估的干预方式。他提到，随着“运动因子（exerkines）”研究的兴起，科学家正逐步揭示身体活动背后的分子机制，这也为将相关生物学发现转化为可规模化的预防策略打开了广阔空间。作为本场讨论的主持人，Life Biosciences首席运营官Michael Ringel博士将衰老定义为人类所面临的最普遍、也最具深远影响的生物学状态。他指出，衰老远比大多数人想象得更早开始，体能和认知功能的可测下降，甚至在生命的第三个十年便已出现。他进一步强调，在发达国家，超过90%的发病率和死亡率都源于与年龄相关的疾病。因此，健康老龄化并非小众的科学议题，而是关乎医疗体系、科研优先级乃至整个社会的核心挑战。阿尔茨海默病：从全球挑战看未来健康作为老年人群中最常见的神经退行性疾病之一，阿尔茨海默病既是“健康老龄化”进程中的严峻挑战，也是一场对生物医药行业创新能力与应对策略的系统性考验。达沃斯阿尔茨海默病协作组织创始主席George Vradenburg先生与F-Prime生物医学研究倡议总裁Stacie Weninger博士，把阿尔茨海默病视作对全球医疗体系的一次“压力测试”。在这场对话中，他们深入探讨科学创新如何实现有效转化，以及如何提升疗法的可及性、可负担性与全球落地能力。 Stacie Weninger博士强调，需要重新思考神经退行性疾病的研究与治疗路径，尤其是在有效疗法仍然有限的领域。她指出，研究本身应当越来越多地发挥“护理”的功能，像肿瘤领域那样，让患者更早获得研究性疗法，从而在满足迫切未满足需求的同时，加速研发进程。她特别强调，生物标志物的快速演进是这一转变的核心驱动力——从最初依赖尸检诊断，到影像学，再到如今的脑脊液和血液标志物，这一系列进展正在根本性地重塑阿尔茨海默病的发现、研究与治疗方式。 George Vradenburg先生则强调了可规模化、低成本技术在改变阿尔茨海默病全球轨迹方面的巨大潜力。他提到，基于语音的认知评估等新工具，有望突破传统临床场景的限制，实现更早期、更广泛的认知障碍识别。通过智能手机、数字平台和远程医疗，这些技术能够将评估、监测与干预真正带到患者身边，从而在全球范围内显著提升脑健康创新的可及性。专题讨论主持、药明康德联席首席执行官杨青博士总结指出，任何挑战都可能转化为机遇，而这些机遇往往会激发科学家提出新的解决方案。同时，尽管任何新技术和新分子在起步阶段往往成本不菲，但随着行业了解的不断加深，我们终将变得更快，更高效，最终造福更广泛的患者群体。塑造未来研发新格局在2026药明康德全球论坛的最后一场专题讨论中，多家知名风险投资机构的代表从投融资视角切入，探讨未来投资方向、技术平台与研发体系应如何演进，才能更好承接新技术浪潮与患者需求。同时，他们也分享了如何通过更高效的协作模式，推动行业取得更快的进展与更优的创新成果。赛诺菲投资董事总经理Jason Hafler先生从务实、以生态体系为先的视角出发，强调大型制药企业在推动创新方面所具备的多元化、灵活工具组合。他指出，创新者与制药伙伴之间保持清晰、透明的沟通至关重要。无论是并购、业务拓展还是股权投资，围绕需求达成共识，都是高效穿越复杂组织结构、加速将药物带给患者的关键。 Flagship Pioneering普通合伙人Avak Kahvejian博士则将行业置于他所称的“生物学世纪”之中，对AI推动药物研发成功率提升持长期乐观态度。他以25年的时间尺度指出，一场低调却深刻的变革已然展开——更理性、更有针对性的研发方式，正逐步降低失败率、压缩成本，并扩大健康寿命改善的全球可及性。 Aulis Capital经营合伙人Nisa Leung女士聚焦当下的融资环境，指出资本纪律已成为成功创新的决定性特征。她认为，真正具备长期影响力与回报潜力的公司，往往由精干、高效、强调执行力与创新精神的创业者所领导。在资金趋紧的环境中，每一美元都必须发挥更大的价值，这不仅塑造着企业行为，也在重塑研发本身的形态。 VZVC联合创始人兼经营合伙人Vijay Pande博士展望了一个公共健康预期发生根本转变的未来——医学将从“治疗疾病”逐步转向“预防疾病”。他认为，预防与长寿将成为医疗体系的重要支柱，而AI在很大程度上将改变医疗服务的经济学基础。尽管这一愿景颇具挑战性，但他强调，其底层基础已在逐步建立。 Sofinnova Partners经营合伙人Henrijette Richter博士强调了欧洲作为全球生物技术创新引擎的崛起。她指出，欧洲长期积累的科研实力，正越来越多地与充沛的私人资本相结合。更大规模的基金、更深层次的协作以及来自美国投资者的持续关注，正共同构成一个正向循环，推动欧洲在全球研发版图中扮演更加重要、开放且具有竞争力的角色。 Canaan Partners普通合伙人Tim Shannon博士则将讨论重新拉回到分子层面，重点介绍了“诱导邻近效应（induced proximity）”这一创新作用机制。他指出，该策略能够解锁传统治疗模式难以触及的全新生物学问题，并以可规模化的小分子方案实现突破。在兼顾创新性、可制造性与成本效率的前提下，这类技术有望将先进疗法惠及更广泛的患者群体。杨青博士也用三个关键词为本场讨论，以及本次药明康德全球论坛做了总结：第一个关键词是“乐观”——在放晴的旧金山，现场切实感受到一种强烈的乐观情绪；第二个关键词是“勇敢新世界”——革命性的技术正深刻改变着整个产业和生态圈；第三个关键词是“振奋”——论坛嘉宾们的分享，也描绘出了通往2026年及未来的巨大机遇。同行致远整场论坛以特邀嘉宾、著名诗人及剧作家Jon Goode先生的思考和灵感作为精神主线，其文字贯穿论坛的开幕、中场与闭幕。通过三个精心编排的篇章，他道出了全球生命科学界共同的目标：真正的创新，不只是技术的飞跃或时间表上的节点，更关乎每一个决策背后所影响的真实人生。他的文字抓住了合作、责任，以及众人携手前行的力量的本质，也让在场的每一位有机会停下脚步，重新思考初心，并再次承诺：我们要做的，是把生的希望，真正变成可及的“治愈性”突破。当论坛接近尾声，他的诗句依然在人们心中回响——它们印证了这一天反复传递的信念：医学的进步，从来不是一个人的孤勇，而是无数人怀着共同使命，并肩前行，为全球患者、家庭和社区一起创造的未来。 WuXi Global Forum 2026: Together, We Advance Breakthroughs for Patients At the dawn of the new millennium in 2000, humanity caught its first glimpse of life’s blueprint. In that defining moment, a dream for medicine was kindled—to understand disease more deeply, to design therapies with greater wisdom, and to bring transformative treatments within reach of countless lives. It was also in that very year that WuXi AppTec was born—founded on a shared vision with innovators around the world, turning that dream into a steadfast commitment. For 25 years, this dream has never remained merely an idea. It has taken root in laboratories, flourished in clinics, and grown steadily through collaboration, trust, and unwavering dedication. Now, standing at the threshold of 2026, the 14th WuXi AppTec Global Forum gathers once again in San Francisco. Dreamers and doers from across the globe reunite under the banner of “B.O.L.D.”—to reflect on a journey of 25 remarkable years, and to gaze toward the dreams still unfolding ahead. To all who have believed in science, championed innovation, and moved medicine forward through action—this is our tribute to you. WELCOME Opening the 14th WuXi Global Forum, Dr. Hui Cai, Program Chair and Vice President of WuXi AppTec, reflected on a journey that began 25 years ago, when science was filled with BOLD ideas and the belief that progress is made by moving forward together. From the optimism of the year 2000 to today’s accelerating pace of discovery, she noted that the advances shaping modern medicine have always been driven by collective courage, shared purpose, and a willingness to act on possibility. Revisiting the Forum’s enduring theme of "BOLD": Breaking barriers, Opening new horizons, Leading the next-generation healthcare solutions, and Delivering on promises for patients, Dr. Cai emphasized that boldness today also means clarity and focus amid a noisy world. The future WuXi AppTec envisions, she underscored, is not built by one company alone, but by a global community advancing together. STATE OF INNOVATION Standing at the beginning of the next 25 years of this century, we are prompted to reflect on the journey so far: what remarkable breakthroughs has the industry achieved, and what bottlenecks still remain to be addressed? In the opening session, “State of Innovation,” a distinguished group of speakers revisited the past, assessed the present, and jointly explored future directions from multiple perspectives, including translational innovation, clinical development, regulation, and investment. Dr. Juergen Eckhardt, EVP, Head of Pharmaceuticals BD&L and Head of Leaps by Bayer, reflected on the emergence of new modalities in the past quarter of century. He said: "I think it was a stunning period, probably unprecedented in terms of new modalities being developed and, most importantly, being made available to patients. It has really changed patient treatment paradigms for many patients in need." While acknowledging the progress, Dr. Kenneth Kaitin, Professor and Senior Fellow at Tufts Center for the Study of Drug Development, also noted that "the process of drug development has remained basically the same for over 60 years, and that's created some interesting challenges for the industry." Among the challenges faced by the industry, improving clinical trial efficiency is on top of many panelists' minds. Dr. Giulio Draetta, SVP and Chief Scientific Officer of MD Anderson Cancer Center, pointed out that contrary to the notion that patients would not want to go through complex clinical trials, there is a lot of generosity coming from the patients and wanting to provide an opportunity for early investigations. Better execution in unifying standard care and clinical trials may dramatically increase the participation of clinical trials. Dr. Mathai Mammen, Chairman, President & CEO of Parabilis Medicines, offered his perspective on clinical trials for rare disease patients. He said: "My advocacy for all patients that suffer from rare diseases would be that companies need to work very hard to use general screening information to find patients that have the condition that's wrong. So that will help substantially in clinical trial conduct for anyone working within anything but well-known diseases." One of the technologies that can be used to improve clinical trials is artificial intelligence (AI). Dr. David Berry, Co-Founder and Managing Partner of Averin Capital offered a tantalizing prospect on the impact of AI on clinical trials. He said with AI, it is possible to do simulations of clinical studies, to the point that the FDA allowed researchers to do a study where they never contacted a patient with drug. Even though replacing clinical trial with AI simulation was considered impossible by many. Speaking of tackling "the impossible", session moderator, Dr. Laura Shawver, Venture Partner at RA Ventures brought up one of her favorite quote, "the difficult we do immediately, the impossible takes a little longer." She believes in the coming years, we will tackle the impossible, whether we believe it's possible today or possible in the future. BREAKING THROUGH IN THE FAST LANE Transforming scientific discovery into therapies that truly benefit patients remains one of the industry’s core challenges. How should we make decisions in advancing innovative medicines? And how can innovation be better aligned with the most pressing unmet medical needs? In the panel discussion “Breaking Through in the Fast Lane,” leaders from several cutting-edge companies shared practical measures and strategies to accelerate drug R&D, challenged traditional development models, and explored new technologies, approaches, and concepts designed to improve both efficiency and success rates. Session moderator, Dr. Jon Edwards, Partner at Forbion, kicked off the discussion by asking "What does speed mean? Is speed raising the most money and having a really large war chest and being able to just move quickly? Is it an experienced team that's not going to make mistakes? Is it AI, which is going to solve all of our problems?" On the prospect of AI in accelerating drug discovery, Dr. Paulo Fontoura, Chief Medical Officer of Xaira Therapeutics said he is an AI optimist. He said: "Obviously AI can accelerate a lot of these things. But it's not just acceleration. It's acceleration to truth finding, and that's really the key thing here. I really think that what AI can do is not only allow us to understand better the biology, but also fit those biologies to the right patients, and therefore deliver more results for them." In addition to AI, Dr. Tony Estrada, President & CEO of Tenvie Therapeutics, emphasized the importance of careful design in clinical trials. He said in the CNS disease space, sometimes moving too fast actually was doing the target and the biology a disservice because then we make incorrect hypotheses or conclusions that set the field back. Panelists also addressed the mindset of how to make better medicines faster. Dr. Sabah Öney, CEO of Dispatch Bio, stressed the urgency demanded by the patients. He said: "We're in solid tumors. Those patients that we are trying to treat are, at the end of life, they have seven or eight months left. They're someone's father, someone's wife, or other sister. And if we are even two years late, that's thousands of patients that we could have impacted but that we didn't impact." Dr. Ken Song, Chairman, President & CEO of Candid Therapeutics, talked about the mindset to design "the right experiment so I can kill the program and shut the company down as fast as I can? If you can't do that, then you have the drug. But if you do the right experiment,you shut the company down fast, then I think that's better. And that makes us more efficient." DELIVERING ON THE PROMISE OF CELL AND GENE THERAPIES As one of the fastest-growing therapeutic modalities in recent years, cell and gene therapies have brought new hope to patients with a wide range of cancers and genetic diseases. In the fireside chat “Delivering on the Promise of Cell and Gene Therapies,” 2025 Nobel Prize in Physiology or Medicine laureate Dr. Fred Ramsdell joined Dr. Jeffrey Bluestone, Founder and Advisor of Sonoma Biotherapeutics to review the historical evolution and current landscape of the field. Together, they discussed how Nobel-winning research on regulatory T-cells has laid the scientific foundation for using cell therapy to treat autoimmune diseases, and looked ahead to future expansion opportunities in cell and gene therapy. Dr. Jeffrey Bluestone noted that Dr. Fred Ramsdell's Nobel winning research revealed that immune tolerance is not the absence of immunity, it's really an active process built on the evolutionary pressures to preserve one's own tissue and allow the immune system to still simultaneously recognize and destroy foreign agents. So regulatory T cells (Tregs) are not accidents of biology, they're actually a lineage that evolved to actually perform these activities and every autoimmune disease that we struggle with, every transplant that's rejected is directly connected to an inability of these cells to do their job the way we want them to do it. So we can now imagine a whole array of drugs that can be developed. Dr. Fred Ramsdell highlighted the difference between Tregs therapy compared to other drug modalities. He said: "What I love about this modality is that we're taking advantage of what evolution has devised to control our immune responses. These cells are really smart, because they had thousands and tens and hundreds of thousands of years to develop to do things. They know where to go and what to do. I can let the cell that's evolved to take care of the tissue, take care of the tissue." WHAT SHOULD WE STRIVE TOWARD FOR PATIENTS Ultimately, scientific breakthroughs and technological advances must translate into meaningful improvements in people’s lives. In the panel “What Should We Strive Toward for Patients” moderated by Dr. Harvey Berger, Chairman & CEO of Arena BioWorks, three scientists with extensive frontline clinical experience — including 2025 Breakthrough Prize laureate Dr. Stephen Hauser, Parker Institute for Cancer Immunotherapy CEO Dr. Karen Knudsen, and Director of Stanford Cardiovascular Institute Dr. Joseph Wu — discussed developments in oncology, cardiovascular disease and neuroscience. They explored which treatment and prevention strategies can truly reshape patient outcomes, and how more patient-centered R&D approaches can drive meaningful, real-world innovation. Session moderator Dr. Harvey Berger opened the discussion by noting that in his opinion, the fundamental problem facing drug discovery and development is the rather high failure rate. "The failure rate is way too high. If that was 50%, speed wouldn't be the issue. We would have a dramatic and profound difference, I think, for patients." Dr. Joseph Wu was optimistic that with advance in technology, the failure rate will hopefully come down in the future. He said: "30-40 years ago, we don't really have access to tissues. Even if we do, all we do is do an H&E staining. Right now you can take the human tissues, do single cell proteomics, single cell sequencing, single nuclear sequencing, figure out exactly what gene goes up, goes down, what proteins are altered. Take those genes and take those proteins, go back to the lab and figure out what type of a drug can modulate that gene, modulate that protein and then go back to the lab again to use all these organoids that we have at our disposal to figure out which one of these really work and then go back to the patient." Dr. Karen Knudsen highlighted the achievements in novel cancer treatments. She said: "We are at the first time in this country that we have a 70% five-year survival rate for all 200 cancers in aggregate. That is an incredible moment. And when you unpack what happens there, it came from innovations in therapeutics in difficult to treat cancers." Dr. Stephen Hauser is hopeful that with the advance in biomarkers, the future for treating neurodegenerative diseases is bright. He said: "These diseases are biologically so much simpler than they were 10 years ago. Alzheimer, Parkinson, ALS, Huntington. We can understand the pathways, understand what can be drug targeted, and I think projects that are very robust, that go after reasonable targets, are going to have a chance to dramatically improve the lives of billions of people." THE FUTURE WE SHARE In his remarks, Dr. Minzhang Chen, Co-CEO of WuXi AppTec, expressed his sincere appreciation to the speakers, customers, partners, investors, and friends who have contributed their insights, trust, and commitment. He reflected on the shared journey that began in 2000, when WuXi AppTec was founded with just four people and a 7,000 square foot chemistry lab, guided by a simple belief that science could change lives. Over the past 25 years, he noted, WuXi AppTec’s growth has been inseparable from the global innovation community that supported it: pushing the boundaries of science, taking risks, and remaining committed through both favorable and challenging times. Reflecting on the session theme, “The Future We Share,” Dr. Chen underscored that the future is never built in isolation; it is shaped by memory, by trust, and by the people who choose to walk the road together. In today’s era of accelerating scientific and technological breakthroughs, he noted, that shared future is taking shape through more than half a million active clinical trials worldwide, each representing a beacon of hope for patients. For WuXi AppTec, this future is both aspirational and deeply practical, powered by over 10,000 medicines currently in the global pipeline, and many more yet to come. It is a future defined not merely by ideas exchanged, but by responsibility embraced, by openness to collaboration, by the courage to advance amid uncertainty, and by a collective commitment to move forward as one community. At the heart of this shared horizon lies a simple yet unwavering principle: to place patients at the center of every decision, and to continue pursuing WuXi AppTec’s enduring vision that “every drug can be made, and every disease can be treated”. SPOTLIGHT ON HEALTHY AGING Population aging is not only a defining global demographic trend, but also a major risk factor for numerous diseases, with profound implications for both life expectancy and quality of life. What does “healthy aging” truly mean? And which breakthroughs have the potential to alter the course of aging-related disease? In the session “Spotlight on Healthy Aging,” experts from academia, biotechnology companies, leading pharmaceutical organizations, and investment institutions came together to discuss strategies for extending healthspan, while exploring the wave of scientific progress now emerging in the field of aging research. Dr. William Greene, Chief Investment Officer at Hevolution Foundation, highlighted a sobering paradox: while lifespan has steadily increased over the past half-century, those added years have largely been accompanied by a growing burden of chronic disease. He noted that the failure to meaningfully bend the curve of age-related illness represents one of the greatest unmet challenges in modern medicine. At the same time, he framed this reality as a powerful opportunity; one that calls for new approaches capable of extending not just how long people live, but how well they live. Dr. Jamie Justice, EVP of Health at XPRIZE Foundation, emphasized the unifying biology underlying many age-related diseases, arguing that aging itself offers a shared target for intervention rather than a collection of isolated conditions. Drawing on evidence from animal models and translational research, she highlighted the growing ability to modulate this biology in ways that could impact multiple diseases simultaneously. She underscored XPRIZE’s focus on advancing these insights into clinical trials, signaling a shift from theoretical promise to real-world validation. Dr. Filip Knop, Chief Medical Officer, SVP Medical & Translational Science at Novo Nordisk, connected emerging longevity science with well-established drivers of healthy aging, pointing to caloric restriction and physical activity as consistent factors across preclinical, epidemiological, and human studies. He described how therapies such as semaglutide may deliver broad benefits by acting on these same biological pathways, reducing caloric intake and supporting physical function. Importantly, he emphasized that growing evidence suggests the relationship between lifespan and healthspan is not fixed, reinforcing the possibility of meaningful intervention. Dr. Eric Verdin, CEO of The Buck Institute for Research on Aging, articulated the central scientific promise of the healthy aging field: that many chronic diseases share common aging-driven mechanisms. He highlighted both animal models and human centenarians as compelling evidence that these mechanisms can be modulated, noting that centenarians spend a remarkably small fraction of their lives affected by age-related disease. This contrast, he argued, offers a powerful proof point that compressing morbidity – and not just extending life – is biologically achievable. Joe Betts-LaCroix, CEO of Retro Biosciences, focused on the emerging biological understanding of interventions that meaningfully improve healthspan, emphasizing caloric restriction, GLP-1 agonists, and physical activity as some of the most impactful levers identified to date. He highlighted exercise as a particularly underutilized intervention, pointing to the growing field of “exerkines” as researchers begin to unravel the molecular mechanisms underlying physical activity. His remarks underscored the breadth of untapped opportunity in translating these biological insights into scalable, preventative strategies. Serving as the session leader, Dr. Michael Ringel, COO of Life Biosciences framed aging as the most universal, and consequential, biological condition facing humanity. He emphasized that aging begins far earlier than most people realize, with measurable declines in physical and cognitive function starting as early as the third decade of life. By underscoring that more than 90% of morbidity and mortality in the developed world stems from age-related diseases, he positioned healthy aging not as a niche scientific pursuit, but as a central challenge for healthcare systems, research priorities, and society at large. ALZHEIMER'S: WHAT A GLOBAL CHALLENGE REVEALS ABOUT THE FUTURE OF HEALTH As one of the most common neurodegenerative diseases among older adults, Alzheimer’s disease represents both a serious challenge within the broader healthy-aging agenda and a critical test of the biopharmaceutical industry’s capacity for innovation and response. Under moderation of Dr. Steve Yang, Co-CEO of WuXi AppTec, George Vradenburg, Founding Chairman of the Davos Alzheimer’s Collaborative, and Dr. Stacie Weninger, President of the F-Prime Biomedical Research Initiative, framed Alzheimer’s disease as a “stress test” for global healthcare systems. Their discussion examined how scientific innovation can be effectively translated into practice and how accessibility, affordability, and global adoption of therapies can be improved. Dr. Stacie Weninger emphasized the need to rethink how neurodegenerative diseases are approached, particularly in areas where effective treatments remain limited. She argued that research itself must increasingly function as a form of care, expanding patient access to investigational therapies earlier, much as oncology has done, in order to accelerate development while addressing urgent unmet needs. Central to this shift, she underscored, is the rapid evolution of biomarkers, noting the field’s progression from post-mortem diagnosis to advanced imaging and, more recently, to CSF and blood-based biomarkers that are fundamentally reshaping how diseases like Alzheimer’s can be detected, studied, and ultimately treated. George Vradenburg highlighted the transformative potential of scalable, low-cost technologies to change the global trajectory of Alzheimer’s disease. He pointed to emerging tools such as blood-spot testing and voice-based detection systems as breakthroughs that could enable early identification of cognitive impairment far beyond traditional clinical settings. By leveraging smartphones, digital platforms, and telehealth, he described a future in which assessment and treatment can reach patients worldwide, bringing detection, monitoring, and care closer to where people live, and fundamentally expanding access to brain health innovation. Dr. Steve Yang, Co-CEO of WuXi AppTec and session leader, pointed out that every challenge has the potential to become an opportunity — an opportunity for scientists to innovate and develop new solutions. Also, the unit cost of new technologies and new modalites could be very high at the beginning. But as the industry moves along the learning curve, we learn to do things faster and more cost-effectively while maintaining the same quality and efficiency. Over time, those costs come down, which in turn drives broader adoption. DEFINING THE NEXT ERA OF R&D In the panel discussion “Defining the Next Era of R&D,” representatives from leading venture capital firms discussed how technology platforms and R&D systems must evolve to meet emerging scientific opportunities and patient needs, and how more effective models of collaboration can help the industry achieve faster progress and deliver better innovative solutions. Dr. Jason Hafler, Managing Director of Sanofi Ventures, framed the future of R&D through a pragmatic, ecosystem-first lens, emphasizing that large pharmaceutical organizations bring a diverse and flexible set of tools to advance innovation. He highlighted the importance of clarity and transparency between innovators and pharma partners, underscoring that alignment on needs, whether through M&A, business development, or equity investment, is critical to efficiently navigating complex organizations and ultimately getting medicines to patients faster. Dr. Avak Kahvejian, General Partner at Flagship Pioneering, situated the industry firmly within what he described as the “biological century,” expressing long-term optimism that advances in AI will dramatically improve the probability of success in drug discovery. Looking out over a 25-year horizon, he pointed to a quiet but meaningful transformation already underway – one in which smarter, more deliberate approaches to R&D are beginning to reduce attrition, lower costs, and enable broader global access to improved healthspan. Dr. Nisa Leung, Managing Partner of Aulis Capital, focused on the realities of today’s funding environment, noting that capital discipline has become a defining feature of successful innovation. She emphasized that the companies poised to deliver both outsized impact and returns are those led by frugal, fast-moving entrepreneurs who prioritize efficiency and innovation. In a constrained funding climate, she underscored that every dollar must work harder, shaping not only company behavior, but the future contours of R&D itself. Dr. Vijay Pande, Co-Founder and Managing Partner at VZVC, looked ahead to a future in which public expectations of medicine fundamentally shift – from treating disease to preventing it altogether. He described prevention and longevity as emerging pillars of healthcare, enabled in large part by AI’s ability to transform the economics of care delivery. While ambitious, he argued that the foundations for this future are already being laid, signaling a broader redefinition of what success in medicine will mean over the next 25 years. Dr. Henrijette Richter, Managing Partner at Sofinnova Partners, highlighted Europe’s growing strength as a global engine of biotech innovation, pointing to its long-standing scientific excellence now increasingly matched by robust private capital. She described a positive, reinforcing cycle – larger European funds, deeper collaboration, and rising interest from U.S. investors – as evidence that Europe’s role in shaping the future of R&D is expanding, collaborative, and globally competitive. Dr. Tim Shannon, General Partner at Canaan Partners, brought the discussion back to the molecular level, spotlighting induced proximity as a powerful example of how next-generation pharmacology can unlock entirely new therapeutic possibilities. He emphasized that this approach enables scalable, small-molecule solutions capable of addressing biological problems beyond the reach of traditional modalities. By combining novelty with manufacturability and cost efficiency, he underscored how such innovations can extend the reach of advanced therapies to large patient populations worldwide. Dr. Steve Yang summarized this panel, as well as the WuXi Global Forum, in three key words. First is optimism: there is a palpable sense of optimism throughout the discussions today. Second is “brave new world”, as transforming technology will fundamentally reshape the entire industry ecosystem. And finally, here and now, it’s clear that there are tremendous opportunities — and real excitement — as we look ahead to 2026. REINFORCING THE SHARED SPIRIT OF INDUSTRY Tying the forum together was a powerful throughline of reflection and inspiration from special guest Jon Goode, whose spoken-word performance wove together the opening, midpoint, and closing moments of the day. Through three thoughtfully crafted segments, he gave voice to the shared purpose that underpins the global life sciences community, reminding the audience that innovation is not only about technologies or timelines, but about the human lives touched by every decision made along the way. His words captured the essence of collaboration, responsibility, and shared strength, offering a moment to pause, reflect, and recommit to advancing breakthroughs that turn hope into healing. As the final notes of the forum settled, his message echoed what the day had made clear: progress in medicine is built together, sustained by purpose, and driven forward for patients, families, and communities around the world. 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

100 项与 Remetinostat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10977	Remetinostat	-	DB14869

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
鲍恩病	临床2期	美国	Medivir AB	2019-12-12
皮肤鳞状细胞癌	临床2期	美国	Medivir AB	2019-12-12
基底细胞癌	临床2期	美国	Medivir AB	2018-07-07
斑秃	临床2期	-	TetraLogic Pharmaceuticals Corp.	2017-02-01
皮肤T细胞淋巴瘤	临床2期	美国	TetraLogic Pharmaceuticals Corp.	2014-11-01
斑块状银屑病	临床1期	澳大利亚	TetraLogic Pharmaceuticals Corp.	2012-09-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03180528 (Pubmed \| Clin Cancer Res) 人工标引	临床2期	基底细胞癌	25	Remetinostat	製蓋糧餘壓鑰積鏇壓鹽(鏇蓋願艱壓範壓廠壓衊) = 襯築襯構餘蓋餘獵觸選壓齋餘遞鹽觸淵淵艱鑰 (憲壓齋獵憲艱夢製願壓 ) 更多	积极	2021-09-01
NCT03875859 (CTgov)	临床2期	鲍恩病 \| 皮肤鳞状细胞癌 \| 鳞状细胞癌	4	Remetinostat	鑰廠膚觸願築蓋鏇觸獵 = 獵衊選積淵齋憲範廠淵艱願網醖鬱糧糧築鑰選 (壓夢壓顧鬱餘齋夢鬱願, 醖繭範襯鏇鹹積鹽夢觸 ~ 願網簾顧選鹽壓艱糧簾) 更多	-	2021-05-20
NCT03180528 (CTgov)	临床2期	基底细胞癌	30	Remetinostat	鹽鹽齋製繭壓膚積窪觸 = 築繭網蓋壓構膚簾襯襯齋簾製膚鬱構顧願選鹽 (蓋鹹製夢鹹壓製廠獵鏇, 醖鏇選醖觸範糧齋範選 ~ 積糧廠襯鹹遞窪艱衊餘) 更多	-	2021-01-05
NCT01433731 (ASCO2014) 人工标引	临床1期	皮肤T细胞淋巴瘤	18	SHP-141	積繭獵窪壓憲鹽構鬱鹽(鑰憲遞蓋積鹽積獵餘憲) = 鑰齋網鏇簾淵觸淵淵選簾壓壓襯艱觸憲餘遞構 (築積積範淵窪襯顧糧艱 ) 更多	积极	2014-05-20
NCT01433731 (ASCO2014) 人工标引	临床1期	皮肤T细胞淋巴瘤	18	placebo	積繭獵窪壓憲鹽構鬱鹽(鑰憲遞蓋積鹽積獵餘憲) = 壓繭鹽憲憲網襯餘膚鹽簾壓壓襯艱觸憲餘遞構 (築積積範淵窪襯顧糧艱 ) 更多	积极	2014-05-20