Phase 1 of the study will open first with a (Bayesian optimal interval BOIN) dose finding design. The starting dose of tomivosertib is 100mgdaily (doses 24 ± 2 hours apart), PO, self-administered with meals. The dose finding follows a BOIN design, with the 100mg BID dose level with a meal being the highest dose. There is one dose level below (dose level -1 = 100mg QD without a meal) that will be given if the de-escalation condition is met during dose finding. Upon completion of the phase 1 dose finding portion of the study, the recommended starting dose of tomivosertib for the subsequent combination with the other agents will be determined, as described in Section 4.3 and Section 8.0.
Tomivosertib will be dosed continuously on days 1-28 of each 28-day cycle at the dose level assigned for that cohort.

开始日期2023-09-29

申办/合作机构

Northwestern University

[+2]

NCT04622007 / Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-Controlled Trial of Tomivosertib in Combination With Anti-PD-(L)1 Therapy in Subjects With NSCLC as First Line Therapy or When Progressing on Single-Agent First-Line Anti PD (L)1 Therapy

Tomivosertib combined with pembrolizumab in Subjects with PD-L1 positive NSCLC

开始日期2021-06-02

申办/合作机构

eFFECTOR Therapeutics Operations, Inc.

[+2]

NCT04261218 / Completed临床1期IIT

A Trial to Assess the Safety, Pharmacodynamic Effects, Pharmacokinetics and Efficacy of the MNK Inhibitor Tomivosertib (eFT508) in Combination With Paclitaxel, Following a Run-in Period of Tomivosertib Monotherapy, in Patients With Advanced Breast Cancer

This is a multicenter, open-label trial to evaluate the safety, pharmacodynamics (PD), pharmacokinetics (PK), and efficacy of tomivosertib in combination with paclitaxel in patients with advanced breast cancer (ABC) of any subtype.
The trial will enroll up to 45 patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 with any breast cancer (BC) subtype and at least one measurable lesion, for whom standard-of-care treatments are ineffective, not tolerated or were refused.
All patients will be initially treated with tomivosertib for 14 days (referred as the run-in period). Once treatment samples are obtained, weekly paclitaxel will be added to the treatment regimen.
Tumor assessments will be done at screening and then periodically throughout trial treatment. Patients will continue to receive trial treatment until progressive disease, as defined according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, intolerable trial-treatment-related toxicity, consent withdrawal, or other criteria is met (defined within the trial protocol).

开始日期2020-08-25

申办/合作机构

Translational Research In Oncology

[+2]

100 项与 MNK 相关的临床结果

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100 项与 MNK 相关的转化医学

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0 项与 MNK 相关的专利（医药）

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项与 MNK 相关的文献（医药）

2024-12-01·Neuropharmacology

Ketamine reverses chronic corticosterone-induced behavioral deficits and hippocampal synaptic dysfunction by regulating eIF4E/BDNF signaling

Article

作者: Gao, Ruyan ; Yang, Canyu ; Li, Axiang ; Li, Shupeng ; Ali, Tahir ; Li, Tao ; Yu, Xiaoming

Major depressive disorder (MDD) is a debilitating illness with a high global burden. While Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, offers rapid-acting antidepressant effects, its mechanism remains incompletely understood. Recent research suggests that dysregulation of mRNA translation via the Eukaryotic initiation factor 4E (eIF4E) pathway might contribute to depression pathophysiology. This study investigates whether Ketamine modulates eIF4E signaling in the hippocampus during its antidepressant action. Herein, adult male mice were exposed to Corticosterone, a well-established model for anxiety and depression, followed by behavioral testing and biochemical analysis. Corticosterone induced depression-like symptoms and disrupted synaptic function, including reduced TrkB/BDNF and eIF4E/MNK1/p-eIF2α/ubiquitin signaling. Ketamine treatment reversed these deficits. Notably, the eIF4E/MNK1 signaling inhibitor, eFT508, blocked Ketamine's antidepressant effect, leading to a return of depression-like phenotype and impaired synaptic signaling. Importantly, these effects were reversed by 7,8-DHF, a BDNF/TrkB signaling agonist. Mice treated with Corticosterone, Ketamine, and eFT508 and subsequently exposed to 7,8-DHF displayed normalized depression-like behaviors and restored synaptic signaling, including increased eIF4E phosphorylation and MNK1 expression. Besides, 7,8-DHF treatment enhanced p-eIF2α levels compared to the eFT508-treated group. These findings suggest that Ketamine exerts its antidepressant action through the regulation of the eIF4E/BDNF signaling pathway in the hippocampus. This study provides novel insights into the molecular mechanisms underlying Ketamine's therapeutic effects and highlights the potential of targeting this pathway for future MDD treatment strategies.

2024-12-01·Computational and Structural Biotechnology Journal

Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer

Article

作者: Zheng, Zicheng ; Ye, Xin ; Sun, Juan ; Ma, Mingwei ; Kang, Weiming ; Li, Jie ; Yu, Tian

Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver (https://pumc.shinyapps.io/GastricCancer/) for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.

2024-11-01·Journal of Neurochemistry

Peripheral and central neuroplasticity in a mouse model of endometriosis

Article

作者: Harrington, Andrea M. ; Maddern, Jessica ; Brierley, Stuart M. ; Erickson, Andelain ; Castro, Joel

AbstractChronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits. Mechanosensitivity of vagina‐innervating primary afferents was examined using an ex vivo single‐unit extracellular recording preparation. Nociceptive signalling from the vagina to the spinal cord was quantified by phosphorylated MAP kinase ERK1/2 immunoreactivity. Immunohistochemistry was used to determine glial and neuronal circuit alterations within the spinal cord. We found that sensory afferents innervating the rostral, but not caudal portions of the mouse vagina, developed mechanical hypersensitivity in endometriosis. Nociceptive signalling from the vagina to the spinal cord was significantly enhanced in mice with endometriosis. Moreover, mice with endometriosis developed microgliosis, astrogliosis and enhanced substance P neurokinin‐1 receptor immunoreactivity within the spinal cord, suggesting the development of neuroinflammation and sensitization of spinal circuitry in endometriosis. These results demonstrate endometriosis‐induced neuroplasticity occurring at both peripheral and central sites of sensory afferent pathways. These findings may help to explain the altered sensitivity to pain in endometriosis and provide a novel platform for targeted pain relief treatments for this debilitating disorder.

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项与 MNK 相关的新闻（医药）

2024-08-15

·药明康德

让“癌症之王”停止生长！《自然》：生酮饮食与药物联用可助力抗癌

▎药明康德内容团队编辑早在古希腊时期，哲学家希波克拉底和柏拉图就在探讨禁食的健康益处。近年来的研究发现，间歇性禁食通过对代谢的重新布局，使得身体的能量供应从葡萄糖转换为酮体，从而带来减轻体重、减少炎症等一系列健康收益。此外，同样以生成酮体为目的的“网红”饮食方式——生酮饮食，也能取得与间歇性禁食相似的效果。生酮饮食摄入的主要能量不再是碳水化合物，取而代之的是大量脂肪。这样一来，身体就会以脂肪代替葡萄糖作为能量供给，靠肝脏分解脂肪产生酮体，为生命活动提供燃料。现在，科学家发现禁食与生酮饮食的这种特质，还能为“癌症之王”胰腺癌的治疗带来新的希望！在近期上线的《自然》论文中，加州大学旧金山分校Davide Ruggero教授带领的团队发现，在使用一种临床试验阶段癌症新药的同时通过生酮饮食喂养，可以“饿死”小鼠体内的肿瘤，让胰腺癌停止生长。虽然禁食对代谢的影响早已有所发现，但一直以来，禁食信号如何在蛋白质组水平上改变基因表达、从而重塑代谢，却缺乏足够的理解。在这项研究中，Ruggero教授团队首先发现，真核细胞翻译起始因子4E（eIF4E）的磷酸化在禁食过程中被诱导。自从被发现以来，eIF4E磷酸化的生理功能始终是未知数。而最新研究揭示了eIF4E如何改变身体代谢，从而在禁食以及生酮饮食期间转换为消耗脂肪来供能。eIF4E磷酸化控制了参与脂质分解代谢以及酮体生成的基因翻译。在禁食或生酮饮食期间，eIF4E磷酸化会通过特定的翻译调控元件来调控肝脏中的信使RNA。相反，抑制eIF4E磷酸化则会损害禁食和生酮饮食引起的酮体生成。 ▲在禁食期间，通过eIF4E磷酸化调控了生酮过程（图片来源：参考资料[1]）有趣的是，研究还发现脂肪酸在这个过程中扮演了意想不到的角色。在禁食或生酮饮食期间，游离的长链脂肪酸含量上升，它们充当了信号分子，激活了营养传感器——AMPK（腺苷酸活化蛋白激酶），AMPK进一步增强了MNK（MAP激酶的相互作用激酶）的磷酸化，而MNK又是eIF4E磷酸化的激酶。到这里，一条由脂肪酸介导的完整信号通路水落石出——AMPK-MNK-eIF4E轴调控着生酮过程，也将生酮与翻译控制联系了起来。图片来源：123RF 在找到这条信号通路后，Ruggero教授意识到，这些发现与癌症治疗产生了奇妙的联系。此前Ruggero教授与合作者共同开发出了一款癌症候选药物——tomivosertib（eFT508）。这种药物分子目前仍在临床试验阶段，其作用原理是MNK1与MNK2抑制剂。科学家们试图将eFT508用于胰腺癌治疗，通过阻断eIF4E的生成，来阻止肿瘤生长。然而，由于葡萄糖、碳水化合物可以维持能量供应，因此胰腺癌可以继续生长。既然如此，通过改变饮食策略、借助使用脂肪供能的生酮饮食，是否可以阻断癌细胞的能量供应、提升eFT508的治疗效果呢？ ▲生酮饮食与eFT508联合抑制肿瘤生长的机制（图片来源：参考资料[1]）在最新研究中，Ruggero教授团队开展了小鼠实验。研究团队首先对小鼠采用生酮饮食，迫使胰腺肿瘤仅消耗脂肪，然后使用癌症药物eFT508。在这种情况下，药物切断了癌细胞仅有的营养供应，肿瘤也缩小了。在此前的临床试验中，eFT508对人体的安全性已经得到证实。现在，最新研究揭示通过eFT508与生酮饮食的联用，能够精确消除胰腺癌。由此，这项研究揭示了胰腺癌的全新弱点，并且发现eIF4E磷酸化的抑制剂可以靶向这一弱点，为饮食干预和小分子药物的联合疗法提供了理论基础。研究团队也推测，在胰腺癌之外，大多数其他癌症也具有各自的弱点，因此将来有望找到更多包含了饮食策略的癌症精准治疗策略。参考资料： [1] Yang et al. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature (2024). https://doi.org/10.1038/s41586-024-07781-7 [2] A ketogenic diet could improve the response to pancreatic cancer therapy. Retrieved Aug. 14, 2024 from https://www.eurekalert.org/news-releases/1054236 本文来自药明康德内容微信团队，欢迎转发到朋友圈，谢绝转载到其他平台。如有开设白名单需求，请在“学术经纬”公众号主页回复“转载”获取转载须知。其他合作需求，请联系wuxi_media@wuxiapptec.com。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。点个“在看”再走吧~

2024-08-15

·奇点网

《自然》：生酮背刺癌王！科学家首次发现，生酮饮食迫使胰腺癌改变代谢方式、暴露致命破绽丨科学大发现

*仅供医学专业人士阅读参考众所周知，生酮饮食是抗癌的“潜力股”。我们之前也成报道过生酮饮食的多种抗癌方式。例如，改善耐药癌细胞对抗癌药的敏感性[1]；降低PD-L1水平，增强CTLA-4抑制剂的抗癌效果[2]；以及生酮饮食产生的酮体β-羟丁酸直接抑制肠癌的形成和发展[3]，等等。虽然阅“机制”无数，但是今天这个抗癌思路，还是让我大呼“过瘾”。今日，由加州大学旧金山分校Davide Ruggero领衔的研究团队（杨浩君是论文的第一作者），在顶级期刊《自然》上发表一项重磅研究成果。他们发现，生酮饮食其实也拿胰腺癌没办法，从正常饮食切换到生酮饮食，胰腺癌照样生长，完全不受影响。不过，他们注意到，胰腺癌为了适应饮食变化，也付出了代价：它通过翻译调控的方式，将自身的代谢方式切换到可以将酮体作为能源的模式。胰腺癌的这一转变，一下子让Ruggero团队看到了破绽：在生酮饮食的同时，用药物阻断胰腺癌的翻译调控通路，就能置胰腺癌于死地。如此看来，对付癌王，懂点儿兵法还是有好处的。 ▲ 论文首页截图说起来，Ruggero团队在一开始的研究计划并不是生酮饮食和胰腺癌，而是禁食是如何改变代谢方式，进而有益健康的。在让小鼠禁食24小时之后，他们发现，真核翻译起始因子4E（eIF4E）的209位丝氨酸磷酸化水平增加，这种磷酸化后的eIF4E（P-eIF4E）处于激活状态。而且，eIF4E唯一已知的激酶MNK，在禁食期间活性也增加。不过，在小鼠开始吃饭之后，P-eIF4E的水平就会降低。显然，eIF4E的活性受进食状态的影响。 ▲ eIF4E的活性受进食状态的影响从转录组的水平来看，在禁食期间，有615个转录本的翻译效率显著上调。这些基因主要参与脂质代谢，其中又以酮体的产生居首位。例如，酮体生成的限速酶Hmgcs2，以及肝脏脂质代谢/酮体生成的主调控因子PPARα等。显然，从进食到禁食的转变改变了肝脏的蛋白翻译格局，特别是增加了参与脂质代谢和酮体生成的基因的翻译。 ▲ 酮体生成排第一那么以上的基因翻译变化是由禁食诱导的P-eIF4E调控的吗？答案是肯定的。定点突变eIF4E第209位丝氨酸（eIF4ES209A）之后，与野生型小鼠相比，禁食24小时的突变鼠产生的β-羟丁酸（BHB，血液中最丰富的酮体）显著减少。而且，之前在禁食时翻译上调的615个基因中，有445个基因在突变鼠的肝脏中显著下调，其中就包括Ppara和Hmgcs2。后续研究还证实，P-eIF4E直接与mRNA的特定区域相互作用，进而完成对蛋白翻译的调节。 ▲ P-eIF4E确实在调控特定基因的翻译在上面的研究中，我们已经知道，禁食激活了MNK-eIF4E通路，导致eIF4E磷酸化被激活，进而改变翻译网络，促进酮体的产生。那么，接下来的问题是：禁食又是如何激活MNK-eIF4E通路的呢？ Ruggero团队注意到，之前已经有研究证实，禁食的主要特征之一是血液中游离脂肪酸（例如棕榈酸、油酸和亚油酸）水平增加，而且这些脂肪酸也可以作为信号分子发挥作用。于是，脂肪酸就成了他们的突破口。在用上述三种脂肪酸处理肝细胞之后，他们发现这些脂肪酸都能激活MNK-eIF4E通路，尤其是亚油酸。然而，这些脂肪酸并不是直接作用于MNK，而是直接与MNK上游的AMPK相互作用，并激活AMPK，继而激活MNK-eIF4E通路。简单来说，就是禁食会增加脂肪酸水平，游离的脂肪酸与AMPK互作并激活AMPK，AMPK随后又磷酸化MNK，被磷酸化激活的MNK再磷酸化eIF4E，促进P-eIF4E的形成，最终调控蛋白的翻译网络，提升酮体水平。 ▲ 通路探秘考虑到生酮饮食也会增加酮体的产生，Ruggero团队想知道背后是不是有类似的机制。他们发现，在将小鼠的饮食换成生酮饮食之后，肝脏中AMPK磷酸化水平和活性增加，P-eIF4E的水平也显著增加。而用药物抑制AMPK活性，则会降低MNK和eIF4E的磷酸化水平。不难看出，P-eIF4E也调控着生酮饮食的酮体产生。这个时候，一种全新的抗癌思路就浮现在Ruggero和他同事的脑海中：有些癌细胞为了生存也会将酮体作为能量来源，如果阻断上面发现的通路，是不是就可以抗癌了。他们先用两种胰腺癌细胞系检验了上述假设。研究结果显示，单独的生酮饮食或者MNK抑制剂（eFT508），都不能抑制肿瘤的生长；而将生酮饮食与MNK抑制剂联合使用，则可以显著抑制肿瘤的生长。 ▲ 生酮饮食（Keto）联合MNK抑制剂（eFT508），有显著抗癌效果究其背后原因，原来是生酮饮食重塑了癌细胞的翻译组，例如癌细胞中MNK-eIF4E通路被激活，生产酮体，在能量不足的情况下，癌细胞就利用酮体供能。而MNK抑制剂（eFT508）恰好阻断了这一过程，让癌细胞在生酮饮食的情况下真的无“粮”可吃。 ▲ 机制示意图总的来说，Davide Ruggero团队的这项研究表明，在禁食/生酮饮食条件下，游离脂肪酸会激活AMPK-MNK-eIF4E通路，进而调节细胞特定基因的翻译水平，重塑细胞的能量代谢方式。据了解，这也是科学家首次发现P-eIF4E参与了翻译调控。对于胰腺癌而言，在生酮饮食的条件下，癌细胞会通过翻译调控的方式重置自己的代谢途径，以适应生酮饮食带来的能量供应不足问题。这不仅揭示生酮饮食对胰腺癌无效的机制，也为生酮饮食联合药物治疗胰腺癌提供了新思路。据了解，MNK抑制剂（eFT508）已经处于临床研究阶段。值得注意的是，除了抗癌之外，Ruggero团队2021年的一项研究成果还显示，eFT508还有治疗肥胖症的潜力[5]。期待Ruggero团队后续的研究成果。参考文献： [1].Hopkins BD, Pauli C, Du X, et al. Suppression of insulin feedback enhances the efficacy of PI3K inhibitors [published correction appears in Nature. 2018 Nov;563(7731):E24. doi: 10.1038/s41586-018-0506-3]. Nature. 2018;560(7719):499-503. doi:10.1038/s41586-018-0343-4 [2].Dai X, Bu X, Gao Y, et al. Energy status dictates PD-L1 protein abundance and anti-tumor immunity to enable checkpoint blockade. Mol Cell. 2021;81(11):2317-2331.e6. doi:10.1016/j.molcel.2021.03.037 [3].Dmitrieva-Posocco O, Wong AC, Lundgren P, et al. β-Hydroxybutyrate suppresses colorectal cancer. Nature. 2022;605(7908):160-165. doi:10.1038/s41586-022-04649-6 [4].Yang, H., Zingaro, V.A., Lincoff, J. et al. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature. 2024. doi:10.1038/s41586-024-07781-7 [5].Conn CS, Yang H, Tom HJ, et al. The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity. Nat Metab. 2021;3(2):244-257. doi:10.1038/s42255-021-00349-z 本文作者丨BioTalker

2024-05-20

·GlobeNewswire-Health Care

eFFECTOR Therapeutics to Collaborate with the Dana-Farber Cancer Institute on an Investigator-Sponsored Phase 2 Clinical Trial Evaluating Zotatifin as Combination Treatment in ER+ Endometrial Cancer and in Low Grade Serous Ovarian Cancer

SOLANA BEACH, Calif. and REDWOOD CITY, Calif., May 20, 2024 (GLOBE NEWSWIRE) -- eFFECTOR Therapeutics, Inc. (NASDAQ: EFTR), a leader in the development of selective translation regulator inhibitors (STRIs) for the treatment of cancer, today announced a collaboration to conduct an investigator-sponsored trial (IST) evaluating zotatifin in combination with abemaciclib and letrozole in patients with estrogen receptor-positive (ER+) endometrial cancer and low grade serous ovarian cancer at the Dana-Farber Cancer Institute (DFCI) under the direction of Panagiotis Konstantinopoulos, M.D., Ph.D., Director of Translational Research and attending oncologist in the Division of Gynecologic Oncology at DFCI, and an Associate Professor of Medicine at Harvard Medical School. “Endometrial cancer is the most prevalent cancer affecting the female reproductive organs in the United States,” said Dr. Konstantinopoulos. “While early detection offers hope for successful treatment, patients with recurrent or metastatic disease have limited treatment options. Recent studies of the abemaciclib and letrozole combo in ER+ endometrial cancer patients have shown promising activity, however, most patients either fail to respond or eventually develop resistance to CDK4/6 inhibition, a critical aspect of treatment. Similarly, low grade serous ovarian cancer has shown sensitivity to combined treatment with aromatase inhibitors and CDK4/6 inhibition, but responding patients eventually develop disease progression. By targeting eIF4A, which subsequently downregulates the key factors implicated in CDK4/6 inhibition resistance, we believe that integrating zotatifin with abemaciclib and letrozole treatment regimen represents a compelling strategy for combating recurrent endometrial cancer and low grade serous ovarian cancer.” Doug Warner, M.D., chief medical officer of eFFECTOR Therapeutics added, “We are thrilled to embark on this investigator-sponsored Phase 2 trial in collaboration with Dr. Konstantinopoulos and his team at the DFCI. This trial represents a significant step forward in our collective efforts to address the complexities of endometrial cancer and low grade serous ovarian cancer. By exploring the potential of zotatifin as a combination treatment and its unique mechanism of action, we aim to redefine the treatment landscape and improve outcomes for these patients. With this comprehensive approach which simultaneously targets tumor cell cycle progression while reducing estrogen levels, we hope to overcome resistance mechanisms and enhance treatment efficacy which we believe could be applied in various malignancies beyond breast and endometrial cancers. In parallel, we continue to advance development of zotatifin in ER+ metastatic breast cancer and anticipate determination of the Phase 2 dose (RP2D) of zotatifin in combination with fulvestrant and abemaciclib, in the second half of 2024.” About Zotatifin Zotatifin is a potent and sequence-selective small molecule inhibitor of the RNA helicase eIF4A that is designed to suppress the overproduction of cell cycle proteins and oncogenes, including Cyclins D and E, CDKs 4 and 6, ERα, KRAS, HER2, and other RTKs. Zotatifin is currently being evaluated in a Phase 2a expansion cohort in combination with fulvestrant and abemaciclib in ER+ breast cancer. Efficacy data presented at 2023 ASCO and SABCS showed a 26% response rate and mPFS of 7.4 months as a triplet in heavily pretreated patients. About eFFECTOR Therapeutics eFFECTOR is a clinical-stage biopharmaceutical company pioneering the development of a new class of oncology drugs referred to as STRIs. eFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase interacting kinase (MNK). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. Each of eFFECTOR’s product candidates is designed to act on a single protein that drives the expression of a network of functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival, and immune evasion. Zotatifin, eFFECTOR’s inhibitor of eIF4A, is currently being evaluated in a Phase 2a expansion cohort in combination with fulvestrant and abemaciclib in ER+ breast cancer and in Phase 2 IST in combination with abemaciclib and letrozole in ER+ endometrial cancer. Tomivosertib, eFFECTOR’s MNK inhibitor, is currently being evaluated in an investigator-sponsored trial in AML. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E. Forward-Looking StatementseFFECTOR cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: the future clinical development of our product candidates, including expectations on enrollment and the timing of reporting data from ongoing clinical trials; the potential therapeutic benefits of our product candidates; and the timing and potential benefits of the IST evaluating zotatifin in combination with abemaciclib and letrozole in patients with ER+ endometrial cancer and low grade serous ovarian cancer. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: potential delays in the commencement, enrollment and completion of clinical trials, including the IST conducted by DFCI; the success of our clinical trials and preclinical studies for our product candidates is uncertain; we are dependent on DFCI to conduct the IST trial and we may not realize any benefits from the collaboration with DFCI; our dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; and other risks described in our prior filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts: Investors: Christopher M. CalabreseManaging DirectorLifeSci Advisors917-680-5608ccalabrese@lifesciadvisors.com Kevin GardnerManaging DirectorLifeSci Advisors617-283-2856kgardner@lifesciadvisors.com Media: Michael Fitzhugh Vice President, Chief of Media StrategyLifeSci Communicationsmfitzhugh@lifescicomms.com

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