Expert opinion on investigational drugs最新文献_第7页

Progress of investigational bromodomain and extra-terminal domain inhibitors for myelofibrosis therapy. 溴结构域和外端结构域抑制剂用于骨髓纤维化治疗的研究进展。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-09 DOI: 10.1080/13543784.2026.2627204

Nooshin C Beygui, Michael Rogers, Veer Shah, Megan Metzger, John Mascarenhas

{"title":"Progress of investigational bromodomain and extra-terminal domain inhibitors for myelofibrosis therapy.","authors":"Nooshin C Beygui, Michael Rogers, Veer Shah, Megan Metzger, John Mascarenhas","doi":"10.1080/13543784.2026.2627204","DOIUrl":"10.1080/13543784.2026.2627204","url":null,"abstract":"Introduction: Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) driven by recurrent acquired somatic mutations in hematopoietic stem cells and characterized by progressive bone marrow fibrosis, cytopenias, and extramedullary hematopoiesis. Janus kinase inhibitors (JAKi) improve splenomegaly and MF symptom burden but without achieving molecular remission or clear disease course modification. Novel therapies targeting epigenetic dysregulation through bromodomain and extra-terminal domain (BET) proteins have emerged as a key therapeutic approach, aimed at reducing pro-inflammatory and oncogenic transcription to deepen clinical responses in combination with JAKi therapy.Areas covered: This review summarizes the biology, preclinical data, and emerging clinical data in the development of novel BET inhibitor (BETi). Trials assessing the efficacy of pelabresib, ABBV-744, INCB057643, BMS-986158, and OPN-2853 are detailed herein.Expert opinion: BET protein inhibition is a promising therapeutic target complementing JAK inhibition by co-targeting inflammatory pathways, fibrosis, and clonal proliferation. Pelabresib is a pan-BETi furthest in development demonstrating clinical benefit with ongoing trials. Research into novel pan-and selective-BETis both as monotherapy and in combination with JAKis or other mechanism-based therapies is ongoing. Whether BETi therapy in MF will ultimately deliver substantial anti-clonal activity to modify disease biology and meaningfully impact clinical outcomes is yet to be determined.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"121-131"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigational agents targeting alarmins for asthma treatment: insights and progress from phase I and II trials. 针对哮喘治疗警报的研究药物：来自I期和II期试验的见解和进展。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-22 DOI: 10.1080/13543784.2026.2619605

Maral Ranjbar, Christiane E Whetstone, Ravneet K Hansi, Fatemeh Sadeghi, Gail M Gauvreau

{"title":"Investigational agents targeting alarmins for asthma treatment: insights and progress from phase I and II trials.","authors":"Maral Ranjbar, Christiane E Whetstone, Ravneet K Hansi, Fatemeh Sadeghi, Gail M Gauvreau","doi":"10.1080/13543784.2026.2619605","DOIUrl":"10.1080/13543784.2026.2619605","url":null,"abstract":"Introduction: Asthma is a chronic and heterogeneous airway disease in which epithelial-derived cytokines - TSLP, IL-33, and IL-25-act as upstream drivers of inflammation. Over the past decade, these alarmin cytokines have become key therapeutic targets, leading to the development of a new generation of biologics designed to intervene early in the inflammatory cascade.Areas covered: This review discusses findings from Phase I and II clinical trials investigating anti-alarmin therapies, including monoclonal antibodies and novel delivery platforms targeting TSLP, IL-33, and IL-25. A comprehensive literature search was conducted across PubMed, ClinicalTrials.gov, and recent conference proceedings to summarize safety, pharmacokinetic, and efficacy outcomes, as well as emerging biomarkers and genetic insights related to treatment response.Expert opinion: Early-phase studies confirm that alarmin blockade is safe, biologically relevant, and efficacious for improving airway inflammation across multiple asthma phenotypes. TSLP inhibition is an approved and clinically available therapy, while IL-33 and IL-25 remain in earlier development. Future progress will rely on optimized airway-focused dosing strategies such as biomarker-guided patient selection and genetic profiling, to achieve optimal personalized therapy. Anti-alarmin biologics are poised to redefine asthma management by addressing inflammation at the epithelial origin of common asthma triggers and advancing clinical care toward precision medicine.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"133-150"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146219144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The latest investigational drugs for patients with allergic rhinitis. 变应性鼻炎的最新研究药物。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-07 DOI: 10.1080/13543784.2025.2612328

Dandan Fang, Yuan Zhang, Luo Zhang

引用次数: 0

Multifunctional antibody-derived IL-12 mimetics: prospects of future clinical development. 多功能抗体衍生的IL-12模拟物：未来临床发展前景。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-11 DOI: 10.1080/13543784.2026.2613289

Britta Lipinski, Lukas Pekar, Andreas Evers, Laura Unmuth, Enrico Guarnera, Stefan Zielonka

{"title":"Multifunctional antibody-derived IL-12 mimetics: prospects of future clinical development.","authors":"Britta Lipinski, Lukas Pekar, Andreas Evers, Laura Unmuth, Enrico Guarnera, Stefan Zielonka","doi":"10.1080/13543784.2026.2613289","DOIUrl":"10.1080/13543784.2026.2613289","url":null,"abstract":"Introduction: Cytokines are important immunomodulatory proteins for therapeutic applications but display several limitations due to their pleiotropic nature, sometimes systemic toxicities, and suboptimal pharmacokinetics. Recent advances in protein engineering have enabled the development of antibody-derived cytokine mimetics which elicit cytokine-like signaling by targeting specific cytokine receptor subunits.Areas covered: In this special report, we summarize our current knowledge of antibody-based cytokine mimetics. We discuss antibody-derived mimetics for several cytokines such as IL-2 an IL-18 and put emphasis on IL-12 receptor agonists with biased cell subset specificities. Furthermore, we provide an overview of next-generation engineering possibilities, including conditionally active cytokine mimetics which convert an anti-inflammatory stimulus into a pro-inflammatory agonism.Expert opinion: Antibody-derived cytokine mimetics represent an emerging class of immunomodulatory agents in a bi- or multispecific architecture which might complement conventional cytokine engineering approaches. While these entities can be highly tailor-made for precise receptor engagement, enabling the modulation of downstream signaling, cell-type specificity, and functional bias, challenges remain, such as potential immunogenicity, preclinical model limitations, and differences in receptor binding affinities compared with natural cytokines.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"1-8"},"PeriodicalIF":4.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PRL3-zumab cancer immunotherapy shows promise for treating neovascular eye diseases. PRL3-zumab癌症免疫疗法有望治疗新生血管性眼病。

IF 4.1 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-10 DOI: 10.1080/13543784.2026.2627206

Koon Hwee Ang, Min Thura, Qi Zeng

引用次数: 0

Advances of next-generation STAMP inhibitors in chronic myeloid leukemia. 新一代stamp抑制剂在慢性髓性白血病中的研究进展。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-23 DOI: 10.1080/13543784.2026.2618980

Alessandro Costa, Massimo Breccia

{"title":"Advances of next-generation STAMP inhibitors in chronic myeloid leukemia.","authors":"Alessandro Costa, Massimo Breccia","doi":"10.1080/13543784.2026.2618980","DOIUrl":"10.1080/13543784.2026.2618980","url":null,"abstract":"Introduction: Specifically Targeting the ABL1 Myristoyl Pocket inhibitors (STAMPi) have reshaped the management of chronic myeloid leukemia (CML). Yet, major challenges remain, including resistance and compound mutations, cross-intolerance, and long-term toxicities. Asciminib has shown efficacy in heavily pretreated patients and in the first-line setting, but resistance and limited benefit after ponatinib highlight the need for new therapeutic options.Covered areas: This review summarizes preclinical and early clinical evidence on next-generation STAMPi. TGRX-678 exhibits potent activity against wild-type and mutant ABL1, including T315I, synergism with orthosteric tyrosine kinase inhibitors (TKIs), central nervous system (CNS) penetration, and encouraging phase Ia/Ib clinical activity in heavily pretreated CML. Early but promising data are also emerging for TERN-701 from the CARDINAL trial.Expert opinion: Next-generation STAMPi may extend therapeutic options beyond asciminib by addressing resistant mutations and enabling rational dual-site inhibition. TGRX-678 ability to achieve CNS exposure raises potential in blast phase CML and Ph+ acute lymphoblastic leukemia. Key questions regarding durability, long-term safety, and optimal integration with ATP-competitive TKIs remain open. Ongoing trials will define the clinical role of these STAMPi and their potential to advance cure-directed strategies, including treatment-free remission.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"99-113"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endoglin-targeted cancer therapies: current status and opportunities. 内啡肽靶向癌症治疗：现状和机遇。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-03 DOI: 10.1080/13543784.2025.2612331

Subinuer Abudukelimu, Hao Dang, Lukas J A C Hawinkels

{"title":"Endoglin-targeted cancer therapies: current status and opportunities.","authors":"Subinuer Abudukelimu, Hao Dang, Lukas J A C Hawinkels","doi":"10.1080/13543784.2025.2612331","DOIUrl":"10.1080/13543784.2025.2612331","url":null,"abstract":"Introduction: Endoglin has been extensively studied as an anti-angiogenic target, with preclinical work highlighting its critical role in tumor vasculature. TRC105 (carotuximab), a monoclonal antibody against endoglin, progressed through multiple clinical trials and was well tolerated, yet outcomes were disappointing, revealing a gap between preclinical findings and patient benefit. Recent insights into endoglin biology in the tumor microenvironment suggest that more precise, informed strategies are needed to fully realize its therapeutic potential.Areas covered: This review summarizes key advances in endoglin biology, including its endothelial and non-endothelial roles and context-dependent effects across tumor and stromal compartments. We discuss preclinical therapeutic strategies and clinical trial experience with TRC105 and examine the translational challenges and future considerations needed to achieve potential clinical benefit.Expert opinion: Preclinical studies have greatly advanced our understanding of endoglin biology, but the key challenge lies in identifying the biologic context where endoglin drives tumor progression. Future progress requires a deeper mechanistic resolution of endoglin's roles across tumor type and disease stage, along with the development of biomarkers incorporating spatial expression patterns. Successful translation will depend on matching endoglin-targeted therapy to patients and tumor ecosystems most likely to benefit, shifting from broad anti-angiogenic application to precision stromal targeting.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"29-36"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Current status and perspective of immunotherapy for head and neck squamous cell carcinoma. 头颈部鳞状细胞癌的免疫治疗现状及展望。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-02-09 DOI: 10.1080/13543784.2026.2627205

Pasquale Vitale, Ilaria Di Giovanni, Chiara Tammaro, Roberta Spedaliere, Evzen Amler, Alois Necas, Marianna Scrima, Michele Caraglia, Raffaele Addeo

{"title":"Current status and perspective of immunotherapy for head and neck squamous cell carcinoma.","authors":"Pasquale Vitale, Ilaria Di Giovanni, Chiara Tammaro, Roberta Spedaliere, Evzen Amler, Alois Necas, Marianna Scrima, Michele Caraglia, Raffaele Addeo","doi":"10.1080/13543784.2026.2627205","DOIUrl":"10.1080/13543784.2026.2627205","url":null,"abstract":"Introduction: Head and neck squamous cell carcinoma (HNSCC), has still a high mortality rate even if several multimodal treatments have been developed in the advanced stages.Areas covered: In recent years, immunotherapy was introduced for the treatment of advanced and metastatic HNSCC with favorable effects on survival and quality of life. Currently, pembrolizumab plus or less chemotherapy is recommended in patients with CPS > 1 in metastatic HNSCC, while nivolumab is used in the second line setting for platinum-refractory disease. However, despite the benefits of these agents, most patients progress after immunotherapy. New approaches to overcome HNSCC immune escape are ongoing, involving antibodies against other immunological locks such as LAG-3, TIGIT, TIM-3, and CD134 (OX40). Moreover, T-lymphocyte activators like GITR and vaccine strategies based on peptides, DNA and RNA against HPV-positive HNSCCs, tumor-associated antigens, dendritic cells, and personalized cancer vaccines have been recently developed.Expert opinion: Future research is crucial to determine the optimal setting for treatment with immunological checkpoint inhibitors through the use of new prognostic biomarkers. This review discusses both completed and ongoing clinical trials with PD-1/PDL-1 and new checkpoint inhibitors and immunotherapies. It also addresses mechanisms of resistance to immunotherapy, potential therapeutic strategies to overcome this resistance, biomarkers and side effects.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"151-168"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A randomized, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics and ammonia-lowering effect of Rifaquizinone, an intestinally restricted investigational drug. 一项随机、双盲、安慰剂对照研究，旨在评估一种肠道限制性研究药物利法齐酮的安全性、药代动力学和降氨效果。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-28 DOI: 10.1080/13543784.2026.2619604

Mengdi Lu, Jing Chen, Hong Zhang, Jia Xu, Xiaojiao Li, Yue Hu, Jingrui Liu, Changlin Ai, Chunhua Shi, Guozhu Geng, Zhenkun Ma, Junqi Niu, Yanhua Ding

{"title":"A randomized, double-blind, placebo-controlled study to evaluate the safety, pharmacokinetics and ammonia-lowering effect of Rifaquizinone, an intestinally restricted investigational drug.","authors":"Mengdi Lu, Jing Chen, Hong Zhang, Jia Xu, Xiaojiao Li, Yue Hu, Jingrui Liu, Changlin Ai, Chunhua Shi, Guozhu Geng, Zhenkun Ma, Junqi Niu, Yanhua Ding","doi":"10.1080/13543784.2026.2619604","DOIUrl":"10.1080/13543784.2026.2619604","url":null,"abstract":"Background: Rifaquizinone (RQZ, TNP-2092) is a novel drug for treating hepatic encephalopathy (HE). This study assessed the safety, pharmacokinetics (PK), and efficacy of RQZ capsules in healthy participants and cirrhosis patients with hyperammonemia.Research design and methods: We conducted three double-blind, randomized, placebo-controlled trials. Trials 1 and 2 enrolled healthy participants, while Trial 3 involved 36 cirrhosis patients with hyperammonemia.Results: In healthy participants and liver cirrhosis patients with hyperammonemia, RQZ was safe and well tolerated. Adverse events were generally mild or moderate. Both food and liver cirrhosis disease status increased the exposure of RQZ, which was around 1% of that of the corresponding doses after intravenous administration. The effect in lowering blood ammonia was dose-dependent. The changes from baseline in blood ammonia levels at day 15 were -14.1 and 0.5 μmol/L in 600 mg and placebo cohort. The percentage of achieving normal blood ammonia during treatment were 31.9% and 7.4% in 600 mg and placebo cohort.Conclusions: Although this study enrolled a relatively small cohort of cirrhotic patients with hyperammonemia, RQZ demonstrated an excellent safety profile as an intestinally restricted agent and showed promising potential for lowering blood ammonia and treating hepatic encephalopathy.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"169-177"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KIF18A inhibition and its rising role in cancer therapy trials: from bench to bedside. KIF18A抑制及其在癌症治疗试验中的作用：从实验到临床。

IF 4.3 2区医学

Expert opinion on investigational drugs Pub Date : 2026-01-01 Epub Date: 2026-01-22 DOI: 10.1080/13543784.2026.2616752

Jia Q Truong, Tal Galper, Jessica K Holien

{"title":"KIF18A inhibition and its rising role in cancer therapy trials: from bench to bedside.","authors":"Jia Q Truong, Tal Galper, Jessica K Holien","doi":"10.1080/13543784.2026.2616752","DOIUrl":"10.1080/13543784.2026.2616752","url":null,"abstract":"Introduction: Chromosomal instability (CIN), a hallmark of over 90% of solid tumors, presents both a vulnerability and an opportunity in cancer therapy. KIF18A, a kinesin motor protein essential for mitotic fidelity, becomes critical for CIN cancer cells, where it suppresses lethal mitotic errors. This selective dependency makes KIF18A an attractive therapeutic target.Areas covered: This review explores the structural and functional biology of KIF18A, its role in maintaining chromosomal alignment, and how its inhibition leads to mitotic failure specifically in cancer cells exhibiting high CIN. We summarize the development of small-molecule inhibitors, from early compounds like BTB-1 to second-generation agents including Sovilnesib and VLS-1488, the latter currently in Phase I/II trials. Clinical data show manageable toxicity and promising antitumor activity, particularly in high-grade serous ovarian cancer. New entrants like ATX-295 and GH2616 further expand the landscape. We also highlight efforts to refine KIF18A targeting through structural studies and emerging AI-driven drug discovery.Expert opinion: KIF18A inhibition represents a mechanistically grounded, tumor-selective strategy for treating CIN-driven cancers. As clinical trials progress, optimizing patient stratification and exploring synergistic combinations will be crucial. Broadening the range of druggable sites on KIF18A, especially beyond the motor domain, could mitigate resistance and help expand therapeutic potential.","PeriodicalId":12313,"journal":{"name":"Expert opinion on investigational drugs","volume":" ","pages":"9-18"},"PeriodicalIF":4.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0