更新于：2024-09-27

Exon 44 Skipping Oligonucleotide(Entrada Therapeutics)

更新于：2024-09-27

概要

研发状态

概要

基本信息

药物类型

反义寡核苷酸

别名

a DMD exon 44 skipping PMO and a proprietary cyclic peptide, EEV, that is designed to enable robust muscle tissue uptake, high cellular internalization and endosomal escape of oligonucleotide therapeutics、exon skipping oligonucleotide、ENTR-601-44

靶点

Nucleic acids

作用机制

Nucleic acids抑制剂(核酸抑制剂)

治疗领域

神经系统疾病遗传病与畸形皮肤和肌肉骨骼疾病+ [1]

在研适应症

杜氏肌营养不良症

非在研适应症-

原研机构

Entrada Therapeutics, Inc.

在研机构

Entrada Therapeutics, Inc.

非在研机构-

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

关联

项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的临床试验

ISRCTN36174912 / Completed临床1期

Phase 1 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Infusion of Ascending Doses of ENTR-601-44 in Healthy Male Volunteers

开始日期2023-08-23

申办/合作机构

Entrada Therapeutics, Inc.

100 项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的临床结果

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100 项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的转化医学

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100 项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的专利（医药）

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项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的文献（医药）

2021-08-01·Journal of molecular neuroscience : MN3区 · 医学

Parkinson Disease-Modification Encompassing Rotenone and 6-Hydroxydopamine Neurotoxicity by the Microtubule-Protecting Drug Candidate SKIP

3区 · 医学

Article

作者: Ivashko-Pachima, Yanina ; Seroogy, Kim B ; Gozes, Illana ; Sharabi, Yehonatan

Encompassing live cell imaging and morphometrics at the microscopical level, we showed here, for the first time, protection of neuronal-like cells by the novel drug candidate, SKIP, against the Parkinson's disease-related neurotoxin, rotenone. Mechanistically, rotenone disrupted microtubule dynamics, which SKIP partially repaired through microtubule end-binding proteins, coupled with increasing neurite branch length. Given the previous association of rotenone toxicity with increased dopaminergic cell death hallmarking Parkinson's disease, we chose an established rat model of 6-hydroxydopamine (6-OHDA) toxicity to initially evaluate SKIP in vivo. SKIP pretreatment showed protection against nigral dopaminergic cell degeneration and improved motor behavior in the forelimb asymmetry test. With Parkinson's disease being a major neurodegenerative disorder, afflicting millions of people globally, and with disease modification challenges, SKIP may hold promise for future therapeutic development.

2016-10-01·Molecular psychiatry1区 · 医学

Sexual divergence in microtubule function: the novel intranasal microtubule targeting SKIP normalizes axonal transport and enhances memory

1区 · 医学

Article

作者: Hacohen-Kleiman, G ; Giladi, E ; Amram, N ; Katz, J ; Pasmanik-Chor, M ; Malishkevich, A ; Lagoudaki, R ; Touloumi, O ; Yeheskel, A ; Sragovich, S ; Grigoriadis, N C ; Jouroukhin, Y ; Gozes, I

Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences. RNA sequencing evaluations showed major age, sex and genotype differences. Function enrichment and focus on major gene expression changes further implicated channel/transporter function and the cytoskeleton. In particular, a significant maturation change (1 month-five months) was observed in beta1 tubulin (Tubb1) mRNA, only in Adnp(+/+) males, and sex-dependent increase in calcium channel mRNA (Cacna1e) in Adnp(+/+) males compared with females. At the protein level, the Adnp(+/-) mice exhibited impaired hippocampal expression of the calcium channel (voltage-dependent calcium channel, Cacnb1) as well as other key ASD-linked genes including the serotonin transporter (Slc6a4), and the autophagy regulator, BECN1 (Beclin1), in a sex-dependent manner. Intranasal SKIP treatment normalized social memory in 8- to 9-month-old Adnp(+/-)-treated mice to placebo-control levels, while protecting axonal transport and ameliorating changes in ASD-like gene expression. The control, all d-amino analog D-SKIP, did not mimic SKIP activity. SKIP presents a novel prototype for potential ASD drug development, a prevalent unmet medical need.

2013-04-01·Neurochemical research3区 · 医学

Spatiotemporal Expression of SKIP After Rat Sciatic Nerve Crush

3区 · 医学

Article

作者: Xiaolong Deng ; Haixiang Wei ; Youhua Wang ; Xinghai Cheng ; Dong Lou ; Hai Wen ; Yajuan Wu ; Long Long ; Hailei Chen ; Jiao Yang ; Hao Wu

Ski-interacting protein (SKIP) is a highly conserved protein from yeast to Human. As an essential spliceosomal component and transcriptional co-regulator it plays an important role in preinitiation, splicing and polyadenylation. SKIP can also combine with Ski to overcome the G1 arrest and the growth-suppressive activities of pRb. Furthermore SKIP has the capacity to augment TGF-β dependent transcription. While the distribution and function of SKIP in peripheral nervous system lesion and regeneration remain unclear. Here, we investigated the spatiotemporal expression of SKIP in an acute sciatic nerve crush model in adult rats. Western Blot analysis revealed that SKIP was expressed in normal sciatic nerves. It gradually increased, reached a peak at 1 week after crush, and then returned to the normal level at 4 weeks. Besides, we observed that up-regulation of SKIP was approximately in parallel with Proliferating cell nuclear antigen (PCNA), and numerous Schwann cells (SCs) expressing SKIP were PCNA and Ki-67 positive. Collectively, we hypothesized peripheral nerve crush induced up-regulation of SKIP in the sciatic nerve, which was associated with SCs proliferation.

项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的新闻（医药）

2024-08-13

·GlobeNewswire-Health Care

Entrada Therapeutics Reports Second Quarter 2024 Financial Results

– Generated positive data from the Phase 1 clinical trial of ENTR-601-44 for DMD, including dose-dependent plasma and muscle concentration, and exon skipping – – Planning underway for separate global Phase 2 clinical trials for ENTR-601-44 and ENTR-601-45 with regulatory filings anticipated in Q4 2024 – – Completed $100 million registered direct offering led by a U.S.-based healthcare focused investor, two global mutual funds and Janus Henderson Investors, a global asset management firm – – Cash runway expected into 2027 with $470 million in cash, cash equivalents, and marketable securities as of June 30, 2024 – BOSTON, Aug. 13, 2024 (GLOBE NEWSWIRE) -- Entrada Therapeutics, Inc. (Nasdaq: TRDA) is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets long considered inaccessible. The Company today reported financial results for the second quarter ended June 30, 2024, and highlighted recent business updates. “In the last quarter, Entrada delivered compelling Phase 1 clinical data from our Duchenne program ENTR-601-44, demonstrating the translation of our nonclinical studies to healthy volunteers. We remain on track to advance separate Phase 2 clinical trials across multiple Duchenne programs, including those targeting exon 44, exon 45 and exon 50,” said Dipal Doshi, Chief Executive Officer at Entrada Therapeutics. “With the completion of a successful financing that extends our cash runway into 2027, we are positioned to advance our Duchenne portfolio while expanding into other disease areas that could benefit from our differentiated approach to intracellular delivery.” Recent Corporate Highlights In June, Entrada announced positive preliminary data from its Phase 1 clinical trial of ENTR-601-44-101 for Duchenne muscular dystrophy (DMD). The study has since been completed with no drug-related adverse findings noted. ENTR-601-44 was generally well-tolerated in healthy volunteers with no serious adverse events, no drug-related adverse events and no clinically significant changes or trends noted in vital signs, electrocardiograms, physical exams or laboratory assessments observed in the trial. The product candidate demonstrated a strong dose-dependent response, significant plasma concentration, muscle concentration and exon skipping, at levels that suggest the potential for a clinically meaningful starting dose in planned upcoming patient trials. Data will be featured in a poster presentation at the 29th Annual Congress of the World Muscle Society, taking place in Prague, Czechia from October 8-12, 2024.Planning is underway for separate global Phase 2 clinical trials for ENTR-601-44 and ENTR-601-45 with regulatory filings anticipated in Q4 2024. The Company also plans to submit regulatory applications in 2025 to initiate a global Phase 2 clinical trial for its third Duchenne candidate, ENTR-601-50, in patients who are exon 50 skipping amenable.The Company completed a $100 million registered direct offering in June 2024. The proceeds from the offering resulted in the extension of the Company’s cash runway into 2027.Vertex Pharmaceuticals announced that they continue to enroll and dose patients in the global Phase 1/2 clinical trial for VX-670 in people with DM1 and expect to complete the single ascending dose (SAD) portion of the study by the end of 2024. Following completion of the SAD portion of the trial, Vertex will move into the multiple ascending dose portion, where both the safety and efficacy of VX-670 will be evaluated. Upcoming Investor Conferences The Company will present at the H.C. Wainwright 25th Annual Global Investment Conference in New York, NY on September 9, 2024. Second Quarter 2024 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $469.7 million as of June 30, 2024, compared to $352.0 million as of December 31, 2023. The increase was primarily a result of the $100 million registered direct offering completed in June of 2024 and the receipt of the $75 million payment for the clinical advancement milestone for VX-670 that was achieved in March of 2024. Based on current operating plans, the Company believes that its cash, cash equivalents and marketable securities as of June 30, 2024 will be sufficient to fund its operations into 2027. Collaboration Revenue: Collaboration revenue was $94.7 million for the second quarter of 2024, compared to $18.2 million for the same period in 2023. The increase was primarily a result of additional VX-670 research activities performed during the second quarter of 2024 and an increase in the total transaction price related to the clinical advancement milestone that was achieved in March of 2024. Research & Development (R&D) Expenses: R&D expenses were $32.0 million for the second quarter of 2024, compared to $26.3 million for the same period in 2023. The increase was primarily driven by additional research activities performed for VX-670 and additional preclinical costs incurred related to ENTR-601-50, as well as higher personnel costs (including non-cash, stock-based compensation). General & Administrative (G&A) Expenses: G&A expenses were $9.2 million for the second quarter of 2024, compared to $8.2 million for the same period in 2023. The increase was primarily due to higher personnel costs (including non-cash, stock-based compensation). Net Income (Loss): Net income was $55.0 million for the second quarter of 2024, compared to a net loss of $(25.9) million for the same period in 2023. About Entrada Therapeutics Entrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets that have long been considered inaccessible. The Company’s Endosomal Escape Vehicle (EEV™)-therapeutics are designed to enable the efficient intracellular delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through this proprietary, versatile and modular approach, Entrada is advancing a robust development portfolio of RNA-, antibody- and enzyme-based programs for the potential treatment of neuromuscular, ocular, metabolic and immunological diseases, among others. The Company’s lead oligonucleotide programs are in development for the potential treatment of people living with Duchenne who are exon 44, 45 and 50 skipping amenable. Entrada has partnered to develop a clinical-stage program, VX-670, for myotonic dystrophy type 1. For more information about Entrada, please visit our website, www.entradatx.com, and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Entrada’s strategy, future operations, prospects and plans, objectives of management, the validation and differentiation of Entrada’s approach and its ability to provide a potential treatment for patients, the translatability of the data from the Phase 1 clinical trial for ENTR-601-44 to future clinical trials for ENTR-601-44, expectations regarding the ability of Entrada’s preclinical studies and clinical trials to demonstrate safety and efficacy of its therapeutic candidates, and other positive results, expectations regarding the starting dose for Entrada’s planned Phase 2 clinical trial for ENTR-601-44, expectations regarding the timing of regulatory filings for the planned Phase 2 clinical trials for ENTR-601-44 and ENTR-601-45 in the fourth quarter of 2024, and ENTR-601-50 in 2025, the ability to recruit for and complete global Phase 2 clinical trials for ENTR-601-44, ENTR-601-45 and ENTR-601-50, the potential of Entrada’s EEV product candidates, including the potential for ENTR-601-44 to be a transformative treatment option, and EEV platform, and the continued development and advancement of ENTR-601-44, ENTR-601-45 and ENTR-601-50 for the treatment of DMD and the partnered product candidate VX-670 for the treatment of myotonic dystrophy type 1, expectations regarding the progress and success of Entrada’s collaboration with Vertex, including express and implied statements regarding any future payments Entrada may receive under the Vertex Agreement, the ability to continue to expand and develop additional therapeutic programs, including further exon skipping programs, the potential therapeutic benefits of its EEV candidates and the ability to advance EEV-therapeutic candidates in indications beyond neuromuscular disease, and the sufficiency of its cash resources into 2027, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Entrada may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the conduct of research activities and the initiation and completion of preclinical studies and clinical trials; uncertainties as to the availability and timing of results from preclinical and clinical studies; the timing of and Entrada’s ability to submit and obtain regulatory clearance and initiate clinical trials; whether results from preclinical studies or clinical trials will be predictive of the results of later preclinical studies and clinical trials; whether Entrada’s cash resources will be sufficient to fund the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements; as well as the risks and uncertainties identified in Entrada’s filings with the Securities and Exchange Commission (SEC), including the Company’s most recent Form 10-K and in subsequent filings Entrada may make with the SEC. In addition, the forward-looking statements included in this press release represent Entrada’s views as of the date of this press release. Entrada anticipates that subsequent events and developments will cause its views to change. However, while Entrada may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Entrada’s views as of any date subsequent to the date of this press release. ENTRADA THERAPEUTICS, INC.Condensed Consolidated Statements of Operations (Unaudited)(In thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Collaboration revenue 94,694 18,170 153,814 43,430 Operating expenses: Research and development 32,035 26,300 60,643 49,402 General and administrative 9,236 8,169 18,635 16,107 Total operating expenses 41,271 34,469 79,278 65,509 Income (loss) from operations 53,423 (16,299) 74,536 (22,079)Other income: Interest and other income 4,366 4,218 8,580 6,875 Total other income 4,366 4,218 8,580 6,875 Income (loss) before provision for income taxes 57,789 (12,081) 83,116 (15,204)Provision for income taxes (2,758) (13,847) (4,589) (17,398)Net income (loss) 55,031 (25,928) 78,527 (32,602)Net income (loss) per share, basic$ 1.61 $ (0.78) $ 2.32 $ (0.99)Net income (loss) per share, diluted$ 1.55 $ (0.78) $ 2.23 $ (0.99)Weighted‑average common shares outstanding, basic 34,180,549 33,163,320 33,838,811 32,770,989 Weighted‑average common shares outstanding, diluted 35,507,029 33,163,320 35,148,221 32,770,989 ENTRADA THERAPEUTICS, INC.Condensed Consolidated Balance Sheet Data (Unaudited)(In thousands) March 31, 2024 December 31, 2023 Cash, cash equivalents and marketable securities$ 469,746 $ 351,969Total assets 581,963 469,192Total liabilities 152,038 226,832Total stockholders’ equity 429,925 242,360 Investor and Media ContactCaileigh DoughertyHead of Investor Relations & Corporate Communicationscdougherty@entradatx.com

临床1期财报临床2期临床结果

2024-06-30

·药明康德

90天内缓解糖尿病的干细胞疗法；治疗乳腺癌临床获益率达60%的CAR-T疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 干细胞疗法VX-880治疗1型糖尿病（T1D）患者在早期临床试验中获得积极数据，在末次随访时12名患者中有11名减少或停止使用外源性胰岛素。 2. 下一代寡核苷酸疗法RGLS8429用于治疗常染色体显性多囊肾病的早期临床试验结果积极，接受3 mg/kg剂量的患者中有70%的肾脏总体积缩小。 3. 通过抗耗竭技术增强的CAR-T细胞疗法LYL797在临床试验中被证明可以浸润到实体瘤中，治疗ROR1阳性复发/难治性三阴性乳腺癌患者的临床获益率（CBR）为60%。药明康德内容团队整理 VX-880：公布1/2期临床试验的新数据 Vertex Pharmaceuticals公司公布了其在研细胞疗法VX-880治疗1型糖尿病的1/2期临床试验的最新数据。VX-880是一种在研干细胞来源、完全分化、产生胰岛素的同种异体胰岛细胞疗法。VX-880有可能通过恢复胰岛细胞功能，包括葡萄糖反应性胰岛素产生，恢复机体调节葡萄糖水平的能力。VX-880通过肝门静脉输注给药，需要长期免疫抑制治疗以保护输入的胰岛细胞免受免疫排斥。VX-880已获得美国FDA授予的再生医学先进疗法（RMAT）认定和快速通道资格，以及欧洲药品管理局（EMA）授予的PRIME资格。公布的结果显示，在接受单次全剂量VX-880输注后90天内，所有T1D患者均显示出胰岛细胞移植成功和对葡萄糖反应的胰岛素生成。在最后一次随访时，12名患者中有11名减少或停止使用外源性胰岛素。Vertex预计增加入组患者数量，并将该疗法推进关键试验阶段。 RGLS8429：公布1b期临床试验的新数据 Regulus Therapeutics公司公布了其开发的新型下一代寡核苷酸疗法RGLS8429用于治疗常染色体显性多囊肾病的1b期临床试验的新数据。常染色体显性多囊肾病是由PKD1或PKD2基因突变引起的，也是最常见的人类单基因疾病之一，同时是终末期肾病的主要原因。RGLS8429旨在抑制miR-17并优先靶向肾脏，在临床前研究中已被证明能够明显改善肾脏功能、大小和其他疾病严重程度指标，并具有优越的药理学特征。此前，该公司已公布1期单次递增剂量临床试验的结果，结果显示，RGLS8429具有良好的安全性、耐受性和药代动力学（PK）特征。此次公布的是1b期研究中第三个队列的结果，患者对RGLS8429的耐受性良好，未发现安全性问题。PC1和PC2是PKD1和PKD2基因的蛋白质产物，已被证明与疾病严重程度呈负相关。接受RGLS8429治疗患者的PC1和PC2与基线相比的百分比变化在所有测试剂量中均显示出缓解，与安慰剂相比，3 mg/kg剂量组具有统计学意义。探索性成像分析表明，3 mg/kg剂量组的患者中，70%的患者肾脏总体积缩小。 LYL797：公布1期临床试验的初步数据 Lyell Immunopharma公司公布了其第一代重编程ROR1靶向CAR-T细胞候选产品LYL797的1期临床试验的初步数据。LYL797采用了Lyell公司的抗耗竭基因重编程技术（c-Jun）和其专有的体外制造方法——表观遗传重编程技术（Epi-R）。LYL797过度表达c-Jun可以纠正耗竭T细胞中AP-1家族转录因子的失衡。在临床前研究中，c-Jun的过度表达使T细胞能够抵抗耗竭、浸润实体瘤并保持其功能。Epi-R技术旨在生成干样T细胞群，减少耗竭，提高增殖和抗肿瘤活性。该研究的初始数据集主要由ROR1阳性复发/难治性三阴性乳腺癌患者组成。结果显示，LYL797对这些患者具有剂量依赖性的抗肿瘤临床活性，患者的客观缓解率为40%，CBR为60%。新闻稿指出，该试验首次证明了通过抗耗竭技术增强的CAR-T细胞既可以增殖又可以浸润到实体瘤中。在无肺部受累的患者中未观察到与LYL797相关的显著安全信号；在肺转移性疾病患者中观察到可治疗的肺炎。根据现有的积极数据，该公司计划扩大开发范围，包括ROR1阳性复发/难治性铂类耐药卵巢癌、子宫内膜癌、多发性骨髓瘤和慢性淋巴细胞白血病等新肿瘤类型。 NTLA-2001：公布1期临床试验的新数据 Intellia Therapeutics公司公布了其CRISPR/Cas9基因编辑疗法NTLA-2001的最新临床数据。NTLA-2001是Intellia与再生元（Regeneron）开展的多靶点发现、开发和商业化合作的一部分，Intellia负责主导NTLA-2001的开发和商业化。之前新闻稿指出，NTLA-2001以CRISPR/Cas9技术为基础，有望成为治疗转甲状腺素蛋白（ATTR）淀粉样变性的首个单次给药疗法。此外，NTLA-2001是首个通过全身给药或静脉注射来编辑人体内基因的候选CRISPR基因编辑疗法，基于Intellia公司专有的非病毒平台，利用脂质纳米颗粒（LNP）向肝脏输送由两部分组成的基因编辑系统：靶向血清转甲状腺素（TTR）基因的特异性gRNA和编码Cas9酶的mRNA。此次公布的结果显示，三位先前在1期剂量递增研究中接受最低剂量NTLA-2001治疗的ATTR淀粉样变性患者，在接受后续55 mg NTLA-2001治疗后，其TTR蛋白水平中位减少90%。根据新闻稿，这是首次临床数据显示体内CRISPR/Cas9基因编辑疗法可有效重复给药，成功完成临床概念验证。 WVE-003：公布1b/2a期临床试验的新数据 Wave Life Sciences公司宣布，在研疗法WVE-003在治疗亨廷顿病（HD）的1b/2a期临床试验SELECT-HD中取得了积极成果。WVE-003是一款等位基因选择性反义寡核苷酸，旨在降低突变亨廷顿蛋白（mHTT）表达并保留健康的野生型亨廷顿蛋白（wtHTT）。数据显示，WVE-003总体安全性和耐受性良好，没有报告严重不良事件。在28周评估期间观察到WVE-003组患者显著的mHTT蛋白水平降低：在24周（最后一次给药后8周），脑脊液（CSF）中mHTT与安慰剂组患者相比平均降低46%（p=0.0007）；在28周（最后一次给药后12周），CSF中mHTT平均降低44%（p=0.0002），支持每季度或更少频率的给药。尾状核萎缩是一个影像学生物标志物，可预测患者的临床结果，包括总运动评分（TMS）的临床显著恶化。在24周（最后一次影像评估）时，mHTT的减少与尾状核萎缩的减缓相关（R=-0.50；p=0.047）。 ENTR-601-44：公布1期临床试验的初步数据 Entrada Therapeutics公司公布了其用于治疗杜氏肌营养不良（DMD）的候选疗法ENTR-601的1期临床试验的积极初步数据。ENTR-601-44是一种专有的内泌体逃逸载体（EEV）偶联磷酸二酰胺吗啉寡聚物（PMO），旨在解决由于DMD基因突变或缺失外显子而导致的DMD的根本原因。ENTR-601-44可用于治疗DMD患者中可跳过44号外显子的患者，目前正在评估其恢复mRNA阅读框的潜力，并允许翻译略有缩短但仍有功能的肌营养不良蛋白。此次公布的结果显示，ENTR-601-44在健康受试者中耐受性良好，没有严重的不良事件，没有与药物相关的不良事件，也没有在生命体征、心电图、体格检查或实验室评估中观察到临床显著的变化或趋势。研究人员在接受ENTR-601-44的患者的肌肉中检测到了药物浓度。与接受安慰剂的患者相比，ENTR-601-44组患者的外显子跳跃水平具有统计学意义。 Divesiran（SLN124）：公布1期临床试验数据 Silence Therapeutics公司宣布，其正在进行的1期临床试验SANRECO获得积极结果。该研究评估了divesiran（SLN124），一种针对TMPRSS6的siRNA，用于治疗真红细胞增多症（PV）患者的安全性和疗效。PV是一种罕见的骨髓增生性肿瘤，其特征是红细胞过量生成，常常导致血细胞比容升高。Divesiran是一款靶向TMPRSS6的siRNA。TMPRSS6是铁调素（hepcidin）的负调节因子，而铁调素是体内铁代谢的主要调节因子，负责铁的吸收、分布和储存。通过在PV患者中沉默TMPRSS6的表达，divesiran旨在增加肝细胞铁调素的生成和释放，从而限制骨髓中的铁含量，减少依赖铁供应的红细胞过度生成。截至2024年3月29日的数据，在16名可评估患者中，8名患者血细胞比容控制良好。这是一项检测血液中红细胞比例的指标。截至目前，divesiran的耐受性良好，没有发现重大安全问题。 Ficerafusp alfa（BCA101）：公布1/1b期临床试验数据 Bicara Therapeutics公司公布了其双功能抗体ficerafusp alfa（BCA101）的1/1b期开放标签剂量扩增研究的最新中期数据。Ficerafusp alfa旨在抑制EGFR并直接在肿瘤部位使TGF-β失效。这种作用机制使得BCA101能够抑制肿瘤增殖，同时恢复局部免疫细胞的细胞毒活性。此次公布的结果显示，ficerafusp alfa与PD-1抑制剂帕博利珠单抗联用，在随访至少12个月的头颈部鳞状细胞癌（HNSCC）患者中显示出有临床意义的抗肿瘤活性，并显著优于标准疗法。在HPV阴性HNSCC患者中，总缓解率为64%（18/28），完全缓解率为18%（5/28），中位无进展生存期为9.8个月，尚未达到中位缓解持续时间和中位总生存期。安全性方面，该联合疗法的耐受性良好，最常见的治疗相关不良事件包括痤疮样皮疹（76%，大多数为1/2级）、疲劳（43%）和低磷血症（38%）。 Lunresertib（RP-6306）：公布1期临床试验的初步数据 Repare Therapeutics公司报告了其PKMYT1抑制剂lunresertib联用FOLFIRI治疗晚期实体瘤患者的1期临床试验的积极数据。Lunresertib是一种潜在“first-in-class”的精准肿瘤学小分子PKMYT1抑制剂，靶向实体瘤中的CCNE1扩增、FBXW7和PPP2R1A变异。截至2024年5月2日的数据，该联合疗法在曾接受过多线治疗、具有CCNE1扩增和FBXW7突变的肿瘤患者中展现出可喜的疗效。不同肿瘤类型患者的总缓解率为18.2%（n=33），包括4例确认和2例未确认的部分缓解，无论既往是否暴露于伊立替康。结直肠癌患者的临床获益延长，40%的伊立替康初治患者接受治疗超过9个月，而该比例的临床基准为20%。安全性方面，lunresertib联合治疗耐受性良好，没有超过单独使用lunresertib或标准FOLFIRI化疗方案的预期毒性。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Vertex Announces Positive Results From Ongoing Phase 1/2 Study of VX-880 for the Treatment of Type 1 Diabetes Presented at the American Diabetes Association 84th Scientific Sessions. 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Retrieved June 26, 2024 from https://www.businesswire.com/news/home/20240624485930/en [21] OrsoBio to Present Phase 1 and Preclinical Data for Liver-Targeted Mitochondrial Protonophore TLC-6740 at the American Diabetes Association’s 84th Scientific Sessions. Retrieved June 26, 2024 from https://www.businesswire.com/news/home/20240621611137/en [22] Biond Biologics Announces First Patient Dosed with BND-35 in Phase 1 Clinical Trial. Retrieved June 26, 2024 from https://www.prnewswire.com/news-releases/biond-biologics-announces-first-patient-dosed-with-bnd-35-in-phase-1-clinical-trial-302180049.html [23] Enlivex Announces the Dosing of the First Patient in a Randomized, Placebo-Controlled Phase I/II Trial Evaluating AllocetraTM in up to 46 Patients with Thumb Osteoarthritis. Retrieved June 26, 2024 from https://www.globenewswire.com/news-release/2024/06/24/2902937/0/en/Enlivex-Announces-the-Dosing-of-the-First-Patient-in-a-Randomized-Placebo-Controlled-Phase-I-II-Trial-Evaluating-AllocetraTM-in-up-to-46-Patients-with-Thumb-Osteoarthritis.html [24] IDEAYA Biosciences Announces First-Patient-In for Phase 1 Clinical Trial Evaluating IDE397 and Trodelvy® Combination in MTAP-Deletion Bladder Cancer. Retrieved June 26, 2024 from https://www.prnewswire.com/news-releases/ideaya-biosciences-announces-first-patient-in-for-phase-1-clinical-trial-evaluating-ide397-and-trodelvy-combination-in-mtap-deletion-bladder-cancer-302181366.html [25] Allakos Announces Positive Results from its Ongoing Phase 1 Trial of AK006 in Healthy Volunteers, with AK006 Demonstrating High Receptor Occupancy on Mast Cells and a Favorable Safety Profile. Retrieved June 26, 2024 from https://www.globenewswire.com/news-release/2024/06/25/2904125/0/en/Allakos-Announces-Positive-Results-from-its-Ongoing-Phase-1-Trial-of-AK006-in-Healthy-Volunteers-with-AK006-Demonstrating-High-Receptor-Occupancy-on-Mast-Cells-and-a-Favorable-Safe.html [26] Werewolf Therapeutics Highlights Initial Safety and Efficacy Data from its Ongoing Phase 1 Clinical Trial Evaluating WTX-330 in Patients with Advanced or Metastatic Solid Tumors or Non-Hodgkin Lymphoma. Retrieved June 26, 2024 from https://www.globenewswire.com/news-release/2024/06/25/2903639/0/en/Werewolf-Therapeutics-Highlights-Initial-Safety-and-Efficacy-Data-from-its-Ongoing-Phase-1-Clinical-Trial-Evaluating-WTX-330-in-Patients-with-Advanced-or-Metastatic-Solid-Tumors-or.html [27] Ethris Announces Positive Initial Phase 1 Data Demonstrating Nasal Delivery of mRNA Lead Candidate ETH47. Retrieved June 26, 2024 from https://www.businesswire.com/news/home/20240624540176/en [28] Revelation Biosciences Announces Phase 1 Clinical Study of Gemini Met the Primary Safety Endpoint and Showed Statistically Significant Biomarker Activity. Retrieved June 26, 2024 from https://www.businesswire.com/news/home/20240624937640/en [29] TiumBio Presents Promising Clinical Data from Phase 1 of its Hemophilia Treatment Candidate TU7710 at ISTH 2024. Retrieved June 26, 2024 from https://www.prnewswire.com/news-releases/tiumbio-presents-promising-clinical-data-from-phase-1-of-its-hemophilia-treatment-candidate-tu7710-at-isth-2024-302180104.html [30] GenVivo Announces Initiation of Patient Dosing in a US Phase I/Ib Clinical Trial Evaluating GEN2, a Personalizing, Gene Vector Immunotherapy, in Patients with Advanced Solid Tumors. Retrieved June 28, 2024, from https://www.globenewswire.com/NC/news-release/2024/06/27/2905012/0/en/GenVivo-Announces-Initiation-of-Patient-Dosing-in-a-US-Phase-I-Ib-Clinical-Trial-Evaluating-GEN2-a-Personalizing-Gene-Vector-Immunotherapy-in-Patients-with-Advanced-Solid-Tumors.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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：本文来自药明康德内容团队，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

细胞疗法临床结果临床1期临床2期寡核苷酸

2024-06-24

·BioSpace

Entrada Therapeutics Announces $100 Million Registered Direct Offering

BOSTON, June 24, 2024 (GLOBE NEWSWIRE) -- Entrada Therapeutics Inc. (Nasdaq: TRDA) is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets long considered inaccessible. The Company today announced that it has entered into a securities purchase agreement with a group of investors for the purchase of 3,367,003 shares of common stock and pre-funded warrants to purchase up to 3,367,003 shares of common stock in a registered direct offering for aggregate gross proceeds of approximately $100 million. The offering was led by a U.S.-based healthcare focused investor, two global mutual funds and Janus Henderson Investors, a global asset management firm. The purchase price for the common stock is $14.85 per share and the purchase price for the pre-funded warrants is $14.8499 per warrant, which represents the per share purchase price for the common stock less the $0.0001 exercise price for the pre-funded warrant. The offering is expected to close on or about June 25, 2024, subject to the satisfaction of customary closing conditions. Entrada expects to use the net proceeds from the offering to fund the ongoing clinical development of each of ENTR-601-44 and ENTR-601-45 through initiation of our planned Phase 2b clinical trials and ENTR-601-50 through initiation of our planned Phase 2 multiple ascending dose trial, the ongoing research and development of our development pipeline (including our neuromuscular and ocular franchises), and the remainder for working capital and other general corporate purposes. The shares of common stock, pre-funded warrants and shares of common stock issuable upon the exercise of the pre-funded warrants were offered pursuant to a “shelf” registration statement that was previously filed with the U.S. Securities and Exchange Commission (the “SEC”) on November 1, 2022 (File No. 333-268099) and declared effective by the SEC on November 7, 2022. A final prospectus supplement containing additional information relating to the offering will be filed with the SEC and will be available on the SEC’s website at . This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction. About Entrada Therapeutics Entrada Therapeutics is a clinical-stage biopharmaceutical company aiming to transform the lives of patients by establishing a new class of medicines that engage intracellular targets that have long been considered inaccessible. The Company’s Endosomal Escape Vehicle (EEV™)-therapeutics are designed to enable the efficient intracellular delivery of a wide range of therapeutics into a variety of organs and tissues, resulting in an improved therapeutic index. Through this proprietary, versatile and modular approach, Entrada is advancing a robust development portfolio of RNA-, antibody- and enzyme-based programs for the potential treatment of neuromuscular, ocular, metabolic and immunological diseases, among others. The Company’s lead oligonucleotide programs are in development for the potential treatment of people living with Duchenne who are exon 44, 45 and 50 skipping amenable. Entrada has partnered to develop a clinical-stage program, VX-670, for myotonic dystrophy type 1. For more information about Entrada, please visit our website, and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding the expected closing of the offering and Entrada’s anticipated use of the net proceeds from the offering constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,” “project,” “potential,” “should,” or “would,” or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including, without limitation, the risks and uncertainties associated with market conditions and the satisfaction of customary closing conditions related to the offering, as well as risks and uncertainties inherent in the Entrada’s business, including those described in Entrada’s periodic filings with the SEC. The events and circumstances reflected in Entrada’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Entrada Therapeutics can be found under the heading “Risk Factors” in Entrada Therapeutics’ periodic reports, including its most recent Form 10-K and in subsequent filings Entrada may make with the SEC, each available on the SEC’s website at Except as required by applicable law, Entrada does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Investor and Media Contact Caileigh Dougherty Head of Investor Relations & Corporate Communications cdougherty@entradatx.com

临床2期

100 项与 Exon 44 Skipping Oligonucleotide(Entrada Therapeutics) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
杜氏肌营养不良症	临床1期	英国	Entrada Therapeutics, Inc.	2023-09-22

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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


ENTR-601-44-101 (Company_Website) 人工标引	临床1期	杜氏肌营养不良症	32	ENTR-601-44	鏇顧築鏇齋衊衊觸構鑰(醖夢齋製觸築鹹齋糧鹹) = None 構簾願餘壓夢遞壓觸鏇 (製糧鏇鹽簾壓艱積夢範 ) 更多	积极	2024-06-24
MDA2023	N/A	-	3	Casimersen	醖獵築鹽積構淵糧襯鹹(願夢網願築醖簾積餘蓋) = Autism spectrum disorder precluded meaningful functional assessment in one ambulatory subject 積餘艱顧網壓蓋憲廠壓 (遞繭糧膚範衊網餘顧齋 ) 更多	积极	2023-03-19
MDA2023	N/A	-	3	Golodirsen		积极	2023-03-19