A Randomized, Double-blinded, Placebo-controlled, Phase 2 Study to Assess the Efficacy and Safety of Three Topical Applications of KH001 in Providing Long-term Relief from Dentin Hypersensitivity

The purpose of this study is to evaluate the efficacy and safety of KH001 in subjects with dentin hypersensitivity.

开始日期2024-10-08

申办/合作机构

Hysensbio Co., Ltd.初创企业

[+1]

NCT06580678 / Not yet recruiting临床2期IIT

A Clinical Study to Evaluate Physiologic Dentin Regeneration When KH001 Was Administration to Erupted Wisdom Tooth With Dentin Caries

The purpose of this study is to evaluate physiologic dentin regeneration and safety of KH001 in the administration of erupted wisdom tooth with dentin caries

开始日期2024-09-13

申办/合作机构

Seoul National University Dental Hospital

[+1]

NCT06264453 / Recruiting临床2期

A Multicenter, Double-blind, Placebo-controlled, Randomized, Parallel-designed, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of KH001 in Patients With Dentin Hypersensitivity

The purpose of this study is to evaluate the efficacy and safety of KH001 in patients with dentin hypersensitivity.

开始日期2024-03-19

申办/合作机构

Hysensbio Co., Ltd.初创企业

100 项与 KH-001 相关的临床结果

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100 项与 KH-001 相关的转化医学

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100 项与 KH-001 相关的专利（医药）

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项与 KH-001 相关的文献（医药）

2023-09-01·Journal of Parasitic Diseases

Novel Schiff bases of Vanillin: potent inhibitors of macrophage harbored Leishmania tropica

Article

作者: Zaman, Ali ; Khan, Sher Wali ; Khan, Rahat Ullah ; Ur Rahman, Mujeeb ; Alam, Naveed ; Khan, Momin ; Sohail, Aamir

Due to limited chemotherapeutic options for leishmaniasis, novel synthetic compounds are gaining attention for evaluation against leishmaniasis. This study aimed to synthesize the compound's Schiff bases of Vanillin to investigate and evaluate their anti-leishmanial potentials against intracellular protozoan parasites Leishmania tropica. In the current study, the phenomena of synergism by designing Schiff bases with Vanillin enhances their desired importance. A total of five compounds Schiff bases of Vanillin were synthesized using different aromatic amines and Vanillin. The structural analysis of all the compounds was done through FT-IR (Fourier Transformer-Infrared), thin layer chromatography, and spectroscopic techniques such as ¹³C-NMR, mass spectrometry, and ¹H-NMR. The antimicrobial properties of all the compounds ZI-1, ZI-2, BS-1, KH-1, and FA-2 against promastigotes and amastigotes forms of L. tropica were analyzed at three different concentrations 25, 50, and 100 µg/ml. The in-vitro MTT assay was performed to calculate the percent inhibition, IC₅₀ values, and their cytotoxicity. The highest percent inhibition values against promastigote form of L. tropica were BS-1 53.78% at 25 µg/ml, ZI-2 66.95% at 50 µg/ml, and again ZI-2 76.92% at 100 µg/ml. Similarly, the highest percent inhibition values against intracellular amastigote stage were BS-1 55.77% at 25 µg/ml, ZI-2 67.78% at 50 µg/ml and again ZI-2 84.93% 100 µg/ml. The highest potency was recorded for BS-1 in both stages, with IC₅₀ values of 9.83 and 4.27 µg/ml against promastigotes and intracellular amastigotes, respectively. The percent hemolysis as toxicity; the lowest percent hemolysis was recorded for ZI-1 at three different concentrations of 25, 50, 100 µg/ml of 2.60, 3.50, and 6.31, respectively. These results suggested that all the compounds exhibited anti-leishmanial activity, with BS-1 as the most potent. Further studies are suggested to increase the activity of compounds with structural modifications by the addition of some other synergistic, novel, and analogue compounds.

2019-01-01·Journal of Controlled Release1区 · 医学

Drug-free albumin-triggered sensitization of cancer cells to anticancer drugs

1区 · 医学

Article

作者: Li, Lian ; Kopeček, Jindřich ; Soodvilai, Sirima ; Opanasopit, Praneet ; Yang, Jiyuan ; Wang, Jiawei

Chemosensitization strategies have been used to sensitize cancer cells to conventional drugs, but their utility is often obstructed by additional off-target toxicity, limited access to intracellular targets and heterogeneous tumor pathogenesis. To address these challenges, we rationally developed a drug-free human serum albumin (HSA)-based therapeutic (KH-1) that functions extracellularly and exhibits pleiotropic effect on multiple intracellular signaling pathways. It is a two-step touch-trigger system that consists of a pretargeting anchor on surface receptor CD20 (anti-CD20 Fab' conjugated with a morpholino oligonucleotide 1) and a CD20 clustering actuator (HSA grafted with multiple copies of complementary morpholino oligonucleotide 2). The extracellular actuation by surface CD20 crosslinking boosts robust activations of numerous intracellular responses, and promotes cancer cell susceptibility to various anticancer drugs, including docetaxel (microtubule stabilizer), gemcitabine (nucleoside analogue) and GDC-0980 (PI3K/mTOR inhibitor). The broad applicability of KH-1 is demonstrated to result from simultaneous inhibition of survival pathways and augmentation of apoptotic pathways. In addition, KH-1 covalently conjugated with anthracycline anticancer agent, epirubicin, integrates the advantages of both chemosensitization function and improved intracellular drug delivery in a single system and takes effect on the same cell. Therefore, in the present study, we have provided mechanistic demonstration that crosslinking of surface receptors can be leveraged to elicit chemosensitization.

2014-08-01·Clinical Infectious Diseases1区 · 医学

Causes and Determinants of Mortality in HIV-Infected Adults With Tuberculosis: An Analysis From the CAMELIA ANRS 1295-CIPRA KH001 Randomized Trial

1区 · 医学

Article

作者: Kim, Chindamony ; Laureillard, Didier ; Marcy, Olivier ; Blanc, François-Xavier ; Dim, Bunnet ; Goldfeld, Anne E ; Sok, Thim ; Borand, Laurence ; Prak, Narom ; Chan, Sarin ; Mayaud, Charles ; Hak, Chanroeurn ; Madec, Yoann ; Delfraissy, Jean-François ; Lak, Kim Khemarin

BACKGROUNDShortening the interval between antituberculosis treatment onset and initiation of antiretroviral therapy (ART) reduces mortality in severely immunocompromised human immunodeficiency virus (HIV)-infected patients with tuberculosis. A better understanding of causes and determinants of death may lead to new strategies to further enhance survival.METHODSWe assessed mortality rates, causes of death, and factors of mortality in Cambodian HIV-infected adults with CD4 count ≤200 cells/µL and tuberculosis, randomized to initiate ART either 2 weeks (early ART) or 8 weeks (late ART) after tuberculosis treatment onset in the CAMELIA clinical trial.RESULTSSix hundred sixty-one patients enrolled contributed to 1366.1 person-years of follow-up; 149 (22.5%) died. There were 8.3 deaths per 100 person-years (95% confidence interval [CI], 6.4-10.7) in the early-ART group and 13.8 deaths per 100 person-years (95% CI, 11.2-16.9) in the late-ART group (P = .002). Tuberculosis was the primary cause of death (28%), followed by other HIV-associated conditions (19%). Factors independently associated with mortality in the first 26 weeks were the age, body mass index, hemoglobin, interrupted or ineffective tuberculosis treatment before identification of drug resistance, disseminated tuberculosis, and nontuberculous mycobacterial disease. After 50 weeks in the trial, the most frequent causes of death were non-HIV related or tuberculosis related, including drug toxicity; factors associated with mortality were late ART, loss to follow-up, and absence of cotrimoxazole prophylaxis.CONCLUSIONSDespite ART introduction, mortality remained high, with tuberculosis as the leading cause of death. Reducing tuberculosis-related mortality remains a challenge in resource-limited settings and requires innovative strategies. Clinical Trials Registration. NCT00226434.

项与 KH-001 相关的新闻（医药）

2023-11-26

·药明康德

晚期实体瘤ORR达41.7%的BRAF小分子抑制剂；创新细菌肽免疫疗法有效治疗胶质母细胞瘤… | 一周盘点

▎药明康德内容团队编辑本期看点1. 创新细菌肽免疫疗法联合免疫检查点抑制剂在进展/复发性胶质母细胞瘤患者中展现强大疗效，患者中位生存期达14.5个月，中位缓解持续时间为13.1个月。2. 新型口服小分子NLRX1激动剂治疗溃疡性结肠炎效果显著，总体梅奥评分和症状缓解方面都出现了持续、快速的临床改善。3. Karuna Therapeutics的精神分裂症药物KarXT安全性良好，不会造成有临床意义的血压升高。4. 下一代BRAF突变体选择性抑制剂显著改善了患有BRAF V600突变型晚期实体瘤患者的预后，总缓解率（ORR）达41.7%。药明康德内容团队整理VMB-100：IND申请获得许可Versameb公司宣布，美国FDA已批准VMB-100的IND申请，用于治疗压力性尿失禁。VMB-100是一种编码人胰岛素样生长因子-1（IGF-1）的工程化mRNA分子，可通过肌肉局部给药。压力性尿失禁是一种非常常见的疾病，由于尿道括约肌功能减弱而导致尿液不自主漏出。临床前研究表明，VMB-100能诱导人体肌肉细胞中IGF-1的表达。在压力性尿失禁动物模型中，VMB-100加快了尿道括约肌的再生，并在单剂量治疗后恢复了尿道括约肌的功能。Versameb公司计划于2024年上半年在患有中度压力性尿失禁的女性受试者中开展VMB-100的2a期开放标签、剂量递增临床研究。VBI-1901：公布1/2a期临床试验数据VBI Vaccines公布了其癌症疫苗候选药物VBI-1901在复发性胶质母细胞瘤（GBM）患者中进行的1/2a期临床研究中获得的更多生物标志物数据。VBI-1901是一种新型癌症疫苗，采用VBI公司的包膜病毒样颗粒（eVLP）技术开发，可靶向两种高免疫原性多巨细胞病毒（CMV）抗原——gB和pp65。新的机制验证数据表明，接种VBI-1901与T细胞活化有关，使得T细胞能穿过血脑屏障进入肿瘤微环境，而肿瘤微环境是一个众所周知的高度免疫抑制、免疫细胞难以浸润的区域。此次公布的外周生物标记物数据评估了C4G的水平——这是细胞毒性T细胞迁移至、并在整个肿瘤微环境中运动时产生的一种蛋白质片段。在既往针对转移性黑色素瘤患者进行的研究中，高基线水平的C4G被发现与较长的总生存期有关。此次公布的数据显示，接种VBI-1901后，实现部分肿瘤缓解的患者血液/血浆中的C4G水平高于病情稳定或进展的患者。此外，接种VBI-1901后，较高水平的C4G与较长的无进展生存期有关。美国FDA认为，与随机对照组相比，治疗组总体生存期在统计学上有显著改善且具有临床意义，并将此作为支持批准新肿瘤药物的标准。Enterome：公布1/2期临床试验数据Enterome公司公布了其1/2期临床试验——EO2401联合免疫检查点抑制剂（纳武利尤单抗）+/-抗VEGF疗法（贝伐珠单抗）治疗首次进展/复发性胶质母细胞瘤患者（ROSALIE试验）的最新疗效数据。11月17日，在神经肿瘤学会（SNO）年会上，该公司作了口头报告。EO2401是一款现货型癌症免疫疗法，它结合了三种细菌肽，这些肽分子来源于肠道微生物群中的细菌，与实体瘤和液体瘤中过表达的肿瘤相关抗原（TAA）或种系特异性标记物密切相似。此外，EO2401还含有CD4辅助肽UCP2。该疗法旨在激活原有的效应记忆T细胞，从而对癌症产生快速、靶向的细胞毒反应。EO2401与纳武利尤单抗和贝伐珠单抗联合用于26例复发性胶质母细胞瘤患者（队列3）。试验结果显示，该联合疗法的耐受性良好，安全性与纳武利尤单抗和贝伐珠单抗一致，只是局部用药部位不良反应略有增加。该联合疗法取得了积极结果：患者中位生存期为14.5个月，中位缓解持续时间为13.1个月，中位无进展生存期（PFS）为5.5个月；第12个月和第18个月的生存率分别为57.4%和43.1%。EO2401与纳武利尤单抗治疗组合对其所靶向的肿瘤相关抗原（IL13Rα2、BIRC5/survivin和FOXM1）产生了快速、强烈和持久的全身免疫应答。队列3中，23名患者对EO2401产生了特异性CD8+T细胞应答，所有这些患者的CD8+T细胞都与其所靶向的TAA产生了交叉反应。HB-500：IND申请获得许可HOOKIPA Pharma宣布其用于治疗人类免疫缺陷病毒（HIV）的新型沙粒病毒治疗性疫苗HB-500的IND申请已获得美国FDA的批准。HB-500是一种双载体沙粒病毒治疗性疫苗，用于治疗HIV感染。一种载体以淋巴细胞性脉络丛脑膜炎病毒（LCMV）为骨架，另一种载体以Pichinde病毒（PICV）为骨架。基于这两种载体的核酸载荷编码相同的HIV抗原。双载体交替使用的方法旨在进一步集中针对目标抗原的免疫反应。HB-500的临床前研究结果最近发表在学术期刊Vaccines上，该研究为提交IND申请奠定了基础。在非人灵长类动物中，该疫苗接种的耐受性良好，并能产生强大、高质量和持久的免疫反应（抗原特异性T细胞和抗体）。与安慰剂相比，接种疫苗可显著降低这些动物体内的类人免疫缺陷病毒（作为HIV的实验替代物模拟其作用）的病毒载量和临床病症。HB-500是HOOKIPA公司与吉利德科学（Gilead Sciences）签订的研发合作和许可协议中两个独立开发项目之一。HOOKIPA公司负责通过完成1b期临床试验来推进HIV项目。此后，吉利德拥有进一步开发该项目的专有权。NX-13：公布1b期临床试验数据Landos Biopharma在学术期刊Journal of Crohn's and Colitis上发表了NX-13治疗溃疡性结肠炎的1b期临床试验的安全性、耐受性、药代动力学特征和临床疗效结果。NX-13是该公司开发的一种新型口服小分子NLRX1激动剂，NLRX1是一种具有调节免疫反应能力的线粒体相关受体，通过激活NLRX1通路可以增加免疫细胞中的氧化磷酸化、减少效应CD4+ T细胞的分化，并减少胃肠道中炎性细胞因子的产生。研究发现，大多数患者在接受为期四周的NX-13治疗后，在总体梅奥评分和症状缓解（以直肠出血和大便次数来衡量）方面都出现了持续、快速的临床改善。此外，试验中观察到的内镜改善与症状改善密切相关。所有患者对NX-13的耐受性良好，没有出现死亡或严重不良反应的报告，所有不良反应均为轻度至中度。KarXT：公布1b期临床试验数据Karuna Therapeutics公布了为期八周的1b期开放标签的住院患者试验的积极结果，该试验评估了KarXT（xanomeline-trospium）对成人精神分裂症患者24小时非卧床血压的影响，试验结果表明KarXT与血压升高无关。KarXT是一款在研口服M1/M4型毒蕈碱乙酰胆碱受体激动剂，由xanomeline和trospium chloride两种有效成分构成，旨在激活大脑中的毒蕈碱型乙酰胆碱受体的同时，减少对外周毒蕈碱型乙酰胆碱受体的作用。这款疗法由Karuna Therapeutics开发，再鼎医药（Zai Lab）拥有这款创新疗法在大中华区的研发权益。该试验的主要终点是第8周时24小时平均非卧床收缩压与基线相比的变化。试验结果表明，受试者24小时动态收缩压从基线到第8周的平均变化为-0.59 mmHg。从基线到第8周的平均血压变化的双侧95%置信区间的上限为1.60 mmHg，这一结果排除了因KarXT治疗造成的有临床意义的血压升高（根据FDA指南，与基线相比的变化≥3 mmHg即为有临床意义的血压升高）。白天和夜间的收缩压测量结果显示没有明显变化，与24小时平均值基本一致。试验中收集的其他生命体征测量数据，包括24小时平均舒张压和心率，与之前针对精神分裂症患者进行的KarXT试验结果一致。此外，KarXT的耐受性总体良好，副作用情况与之前的临床试验一致。Plixorafenib：公布1/2a期临床试验数据FORE Biotherapeutics公布了评估plixorafenib（又名FORE8394，PLX8394）的1/2a期临床试验的最新安全性和疗效数据。Plixorafenib是一款可口服的下一代小分子BRAF突变体选择性抑制剂，旨在靶向广泛的BRAF突变，同时不影响野生型RAF蛋白的活性。此次公布的研究结果继续显示了该药物针对BRAF V600突变肿瘤（包括原发性中枢神经系统肿瘤）的单药活性。在9名患有BRAF V600突变的原发性中枢神经系统肿瘤、并且未接受过MAPK抑制剂治疗的患者中，有6人实现了缓解，总缓解率为66.7%（95% CI：29.9，92.5）。此外，中位缓解时间为13.9个月（范围：3.7，32.3），其中4/6（67%）的治疗响应者的缓解时间超过6个月。试验过程中，低级别胶质瘤和胶质神经元肿瘤患者的中位无进展生存期尚未达到（范围：1.6至27.8个月；n=4），高级别胶质瘤患者的中位无进展生存期为6.7个月（范围：2.8至34.1个月；n=5）。在24名患有BRAF V600突变型晚期实体瘤、且未接受过MAPK抑制剂治疗的患者中，有10人达成缓解，总缓解率为41.7%。这些患者的中位缓解时间为17.8个月（范围：3.7至59.2个月）。BRAF V600突变型实体瘤患者（包括之前接受过MAPK抑制剂治疗的患者）的中位应缓解时间为3.5个月。与已获批准的BRAF/MEK抑制剂相比，plixorafenib继续表现出良好的耐受性，出现症状性治疗突发不良事件（TEAE）的频率较低。症状性TEAE几乎均为1级，头痛是唯一的症状性≥3级治疗伴发不良事件，发生率>5%。此外，原发性中枢神经系统肿瘤患者的安全性与总体观察结果一致。AV5124：公布1期临床试验数据Viriom公司公布了新型流感病毒复制抑制剂AV5124的1期临床试验的积极结果。AV5124是一种非常有效的流感病毒RNA处理抑制剂，对所有测试过的流感类型都有很强的抑制作用，包括对神经氨酸苷酶抑制剂Tamiflu或帽依赖性内切酶抑制剂Zoflusa耐药的病毒。最近的1期临床研究结果表明，AV5124具有出色的安全性和耐受性。该研究的血药浓度与单次口服后数天的病毒抑制效果一致。AV5124卓越的安全性和已知的抗流感病毒效力支持将该化合物推进到2-3期疗效研究，该研究将在今年流感季节开始。KH-001：IND申请获得许可美国FDA和英国药品和健康产品管理局（MHRA）分别批准了Kanna Health旗下药物KH-001的新药临床试验申请（IND）和临床试验申请（CTA），以研究KH-001在健康男性受试者中的安全性和药代动力学特征。KH-001是一种独特的、按需定制的药物，是首个获得FDA许可用于早泄治疗的药物。大家都在看▲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] Versameb AG Announces FDA Clearance of IND Application for VMB-100 in the Treatment of Stress Urinary Incontinence，Retrieved November 23, 2023 from https://www.prnewswire.com/news-releases/versameb-ag-announces-fda-clearance-of-ind-application-for-vmb-100-in-the-treatment-of-stress-urinary-incontinence-301990373.html[2] Immix Biopharma Announces FDA Approval of IND Application for CAR-T NXC-201, Enabling U.S. Patient Dosing，Retrieved November 23, 2023 from https://www.biospace.com/article/releases/immix-biopharma-announces-fda-approval-of-ind-application-for-car-t-nxc-201-enabling-u-s-patient-dosing/[3] VBI Vaccines Presents Additional Biomarker Data from Phase 1/2a Study of VBI-1901 in Recurrent GBM at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting，Retrieved November 23, 2023 from https://www.businesswire.com/news/home/20231120733718/en/[4] Enterome’s OncoMimics™ Immunotherapy EO2401 Significantly Improves Survival Rate in Recurrent Glioblastoma，Retrieved November 23, 2023 from https://www.enterome.com/news-events/enterome-oncomimics-immunotherapy-eo2401-significantly-improves-survival-recurrent-glioblastoma/[5] HOOKIPA Pharma Announces FDA Clearance of its Investigational New Drug Application for HB-500 for the Treatment of Human Immunodeficiency Virus，Retrieved November 23, 2023 from https://ir.hookipapharma.com/news-releases/news-release-details/hookipa-pharma-announces-fda-clearance-its-investigational-new[6] ProMIS Neurosciences Doses First Subjects in Phase 1a Clinical Trial of PMN310 to Treat Alzheimer’s Disease，Retrieved November 23, 2023 from https://www.promisneurosciences.com/news-media/press-releases/detail/212/promis-neurosciences-doses-first-subjects-in-phase-1a#:~:text=%E2%80%9CIn%20this%20Phase%201a%20clinical,the%20first%20half%20of%202024.[7] Landos Biopharma Publishes Results of NX-13 Phase 1b Study in Ulcerative Colitis in Journal of Crohn’s and Colitis，Retrieved November 23, 2023 from https://www.biospace.com/article/releases/landos-biopharma-publishes-results-of-nx-13-phase-1b-study-in-ulcerative-colitis-in-journal-of-crohn-s-and-colitis/[8] PureTech Founded Entity Karuna Therapeutics Announces Positive Results from Phase 1b Ambulatory Blood Pressure Monitoring Trial of KarXT in Schizophrenia，Retrieved November 23, 2023 from https://www.businesswire.com/news/home/20231116001299/en/[9] FORE Biotherapeutics Announces Oral Presentation at SNO 2023 Reporting Updated Phase 1/2a Results for Plixorafenib in BRAF V600 Advanced Solid Tumors, Including Novel Data for Patients with BRAF V600 Primary CNS Tumors，Retrieved November 23, 2023 from https://www.businesswire.com/news/home/20231117112617/en[10] Viriom's Single Pill Influenza Treatment Completes Critical Phase I Clinical Trials，Retrieved November 23, 2023 from https://www.prnewswire.com/news-releases/virioms-single-pill-influenza-treatment-completes-critical-phase-i-clinical-trials-301992666.html[11] Kanna Health announces FDA and MHRA approvals to begin its Phase 1 clinical trial for the development of KH-001 as first FDA-approved treatment for premature ejaculation，Retrieved November 23, 2023 from https://www.prnewswire.com/news-releases/kanna-health-announces-fda-and-mhra-approvals-to-begin-its-phase-1-clinical-trial-for-the-development-of-kh-001-as-first-fda-approved-treatment-for-premature-ejaculation-301987933.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

免疫疗法疫苗临床申请信使RNA临床1期

2023-11-19

·药明康德

降解靶蛋白超90%的蛋白降解剂；下一代DMD基因疗法获批临床... | 一周盘点

▎药明康德内容团队编辑本期看点1. 靶向IRAK4的蛋白降解剂KT-474的1期临床结果亮眼，在血液和活动性皮肤病变中具有强大的IRAK4敲低效果，多种给药模式下，血液IRAK4的降解率均超过90%。2. 用于治疗天使综合征的反义寡核苷酸疗法ION582在早期临床研究中显示出令人鼓舞的脑电图（EEG）活动趋势和早期积极临床改善的信号。3. 用于治疗杜氏肌营养不良（DMD）的下一代候选基因疗法SGT-003在美国获批临床，第一批目标患者为4岁-6岁以下的DMD患者。药明康德内容团队整理KT-474：公布1期临床试验数据Kymera Therapeutics公司公布了其用于炎症性疾病的潜在“first-in-class”的IRAK4降解剂KT-474的积极早期临床结果。KT-474通过与IRAK4结合，能够募集E3泛素连接酶给IRAK4打上泛素的“标签”。这些“标签”会指引IRAK4蛋白被细胞的“垃圾回收系统”蛋白酶体降解，从而阻断IRAK4介导的信号传导。此前，赛诺菲（Sanofi）已承诺与Kymera合作，推进KT-474用于治疗化脓性汗腺炎（HS）和特应性皮炎（AD）的2期临床试验。此次公布的结果显示，在健康受试者的血液中观察到IRAK4的降解，单次给药600-1600 mg后，IRAK4的平均降幅≥93%，剂量在50–200 mg，连续给药14天后，IRAK4的平均降幅≥95%。在接受75 mg KT-474治疗的患者中，血液中的IRAK4降解情况相似，并且相对于健康受试者，在皮肤病变中过表达的IRAK4得到了正常化。在HS和AD患者的血液和皮肤中显示了与皮肤病变和症状改善相关的疾病相关性炎症生物标志物的减少。安全性方面，KT-474的耐受性良好，未发现与药物相关的感染。ION582：公布1/2a期临床试验的初步数据Ionis Pharmaceuticals公布了其反义寡核苷酸疗法ION582（BIIB121）早期临床研究的积极初步结果。ION582通过鞘内给药，旨在抑制UBE3A转录本（UBE3A-ATS）的表达，用于治疗天使综合征。Ionis已与渤健（Biogen）达成战略合作，共同开发ION582。该疗法已在美国获得孤儿药资格。此次公布的结果显示，ION582的耐受性良好，并显示出令人鼓舞的EEG活动趋势和早期积极临床改善的信号，但未来仍需要对完整数据集进行分析以确认。在接受第1阶段治疗一个月后的可评估患者中，大多数患者的EEG活动有所改善。天使综合征的临床表现为慢Delta脑波活动的增加，约70%的患者显示出慢波EEG Delta活动减少，超过80%的患者显示出更快频率节律的增加。在临床医生评估的9个关键功能领域的印象评分中，大多数患者显示出整体功能的改善。大多数患者在能直接评估临床功能的Bayley评分上显示出改善。SGT-003：IND申请获得FDA许可Solid Biosciences公司宣布其用于治疗DMD的下一代候选基因疗法SGT-003的IND申请已获得美国FDA的批准，计划在小儿DMD患者中启动1/2期试验，首个队列将针对4岁至6岁以下的患者。SGT-003采用Solid公司专有的的载体（AAV-SLB101）递送编码缩短形式的肌营养不良蛋白——微肌营养不良蛋白（microdystrophin）的DNA序列，其中包含R16和R17 nNos结合蛋白结构域。临床前数据表明，这对于患者肌肉功能和受益的持久性可能至关重要。在DMD小鼠模型中，SGT-003表现出迅速的转导，在基因治疗后的第4天就在心脏、股四头肌和隔肌中表现出强有力的微肌营养不良蛋白的表达。在非人灵长类动物中，相较于使用AAV9作为载体的疗法，SGT-003在心脏和骨骼肌（包括隔肌）中的分布增加。这些研究表明，与第一代微肌营养不良蛋白基因疗法相比，SGT-003具有增加的基因表达和改善的安全性。EHM（工程化的人心肌）：公布1/2期临床试验的初步数据Repairon公司公布了其诱导多能干细胞（iPSC）衍生的工程化的人心肌（EHM）作为终末期心力衰竭患者的生物心室辅助组织（BioVAT）的初步早期临床数据。结果显示，在所有测试剂量下，由iPSC衍生的心肌细胞和基质构建的EHM是安全且耐受良好的。该研究提供了EHM移植物可持续增厚目标心壁的首个证据，以及EHM移植物能够改善心功能（射血分数）和症状的首个证据。PV-10：公布1期临床试验数据Provectus Biopharmaceuticals公布了其癌症免疫疗法PV-10（rose bengal sodium，RBS）用于治疗葡萄膜黑色素瘤（UM）肝脏转移（mUM）患者的1期临床试验的最新数据。PV-10是一种合成小分子免疫催化剂，可在不同浓度下表现出不同的治疗效果，并可通过不同途径进行给药。PV-10具有双功能靶向疾病的特性，直接接触可能导致细胞死亡或修复，具体取决于治疗的疾病和使用的药物浓度，随后可能发生多变的免疫信号、激活和反应，表现为刺激性、抑制性或两者兼而有之。截至新闻稿发布，已有25例mUM患者接受了PV-10单药或PV-10联合标准免疫检查点抑制剂治疗（CB）。此次公布的结果显示，PV-10单药或联合CB的安全性可接受，没有出现死亡或永久性的3级不良事件。研究人员使用2D-EASL成像检测评估了PV-10注射到肝部病灶的疗效，1例（4%）患者达到完全缓解（CR），7例（28%）患者达到部分缓解（PR），客观缓解率（ORR）为32%，8例（32%）患者达到疾病稳定（SD），疾病控制率（DCR）为64%。所有患者的中位总生存期（mOS）为11.0个月，其中，M1a阶段患者的mOS为30.6个月，接受PV-10+伊匹木单抗+纳武利尤单抗联合疗法的M1a阶段患者的mOS长达50.0个月。Zanzalintinib：公布1b期临床试验数据Exelixis公司公布了其新一代口服酪氨酸激酶抑制剂（TKI）zanzalintinib治疗既往接受过治疗的透明细胞肾细胞癌（ccRCC）患者的效果。Zanzalintinib可抑制与癌症生长和扩散有关的受体酪氨酸激酶的活性，包括VEGF受体、MET、AXL和MER。这些受体酪氨酸激酶参与正常细胞功能和病理过程，如肿瘤发生、转移、肿瘤血管生成和对多种疗法（包括免疫检查点抑制剂）的耐药性。此次公布的结果显示，在中位随访时间为8.3个月时，32名加入扩展队列的患者中有12人达到了确认的PR，ORR为38%，DCR为88%。▲按既往疗法分组划分的其他疗效结果（图片来源：参考资料[3]）数据截止时，50%的患者仍在继续接受治疗。未接受过卡博替尼治疗患者的中位缓解持续时间为7.4个月，接受过卡博替尼治疗的患者的中位缓解持续时间尚无法估计。大家都在看▲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] Kymera Therapeutics Announces Publication of Phase 1 Trial Results for KT-474 (SAR444656), a First-in-Class IRAK4 Degrader, in Nature Medicine. Retrieved November 14, 2023, from https://www.globenewswire.com/news-release/2023/11/13/2779228/0/en/Kymera-Therapeutics-Announces-Publication-of-Phase-1-Trial-Results-for-KT-474-SAR444656-a-First-in-Class-IRAK4-Degrader-in-Nature-Medicine.html[2] Primmune Therapeutics Presents Clinical Data from Phase 1 Study Evaluating PRTX007 in Healthy Volunteers at the 2023 American Association for the Study of Liver Diseases (AASLD) Annual Meeting. Retrieved November 14, 2023, from https://www.businesswire.com/news/home/20231110452221/en[3] Exelixis Announces Encouraging Results from Expansion Cohort of Phase 1b STELLAR-001 Trial Evaluating Zanzalintinib in Patients with Advanced Kidney Cancer at IKCS 2023. Retrieved November 14, 2023, from https://www.businesswire.com/news/home/20231106261142/en[4] Astria Therapeutics Presents New Phase 1a Data Confirming Potential for STAR-0125 to Prevent Hereditary Angioedema Attacks with Dosing 2 or 4 Times Per Year at the 2023 American College of Allergy, Asthma, and Immunology Annual Scientific Meeting. Retrieved November 14, 2023, from https://www.businesswire.com/news/home/20231110656373/en[5] AskBio Presents Preliminary Data from Phase 1 Trial of Gene Therapy for Congestive Heart Failure (CHF) at the 2023 American Heart Association Scientific Sessions. Retrieved November 14, 2023, from https://www.prnewswire.com/news-releases/askbio-presents-preliminary-data-from-phase-1-trial-of-gene-therapy-for-congestive-heart-failure-chf-at-the-2023-american-heart-association-scientific-sessions-301985319.html[6] Ionis shares positive clinical update from ongoing trial of ION582 for Angelman syndrome. Retrieved November 14, 2023, from https://www.prnewswire.com/news-releases/ionis-shares-positive-clinical-update-from-ongoing-trial-of-ion582-for-angelman-syndrome-301985239.html[7] PROVECTUS BIOPHARMACEUTICALS PROVIDES UPDATED DATA ON CANCER IMMUNOTHERAPY PV-10 FOR METASTATIC UVEAL MELANOMA. Retrieved November 14, 2023, from https://www.provectusbio.com/news/press-releases/provectus-biopharmaceuticals-provides-updated-data-on-cancer-immunotherapy-pv-10-for-metastatic-uveal-melanoma/[8] Solid Biosciences Announces IND Clearance by FDA for Duchenne Muscular Dystrophy Gene Therapy Candidate SGT-003. Retrieved November 14, 2023, from https://www.globenewswire.com/news-release/2023/11/14/2780518/0/en/Solid-Biosciences-Announces-IND-Clearance-by-FDA-for-Duchenne-Muscular-Dystrophy-Gene-Therapy-Candidate-SGT-003.html[9] BioVAT-HF Phase 1/2 Reveals First Evidence for Effective Heart Repair in Advanced Heart Failure. Retrieved November 14, 2023, from https://www.globenewswire.com/news-release/2023/11/14/2779689/0/en/BioVAT-HF-Phase-1-2-Reveals-First-Evidence-for-Effective-Heart-Repair-in-Advanced-Heart-Failure.html[10] Kanna Health announces FDA and MHRA approvals to begin its Phase 1 clinical trial for the development of KH-001 as first FDA-approved treatment for premature ejaculation. Retrieved November 17, 2023, from https://www.prnewswire.com/news-releases/kanna-health-announces-fda-and-mhra-approvals-to-begin-its-phase-1-clinical-trial-for-the-development-of-kh-001-as-first-fda-approved-treatment-for-premature-ejaculation-301987933.html[11] Karuna Therapeutics Announces Positive Results from Phase 1b Ambulatory Blood Pressure Monitoring Trial of KarXT in Schizophrenia. Retrieved November 17, 2023, from https://www.businesswire.com/news/home/20231116835102/en[12] Alentis Therapeutics Doses First Patient in Phase 1/2 Clinical Trial of ALE.C04 in Head and Neck Squamous Cell Carcinoma (HNSCC). Retrieved November 17, 2023, from https://www.businesswire.com/news/home/20231116577905/en/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

临床1期临床2期寡核苷酸临床结果孤儿药

2022-06-30

·PRNewswire

Kanna Health announces publication of patent application for KH-001 as a treatment for premature ejaculation

LONDON, June 30, 2022 /PRNewswire/ -- Kanna Health Ltd (Kanna Health) - Today, the World Intellectual Property Office has published Kanna Health's patent application covering the use of KH-001 as a treatment for premature ejaculation, entitled "Methods for delay of ejaculation in human males" (WO/2022/140417). KH-001 is a unique proprietary form of a naturally-occurring alkaloid. Scientists at Kanna Health have elucidated the pharmacological targets of KH-001. Based on these data, Kanna Health demonstrated that KH-001 significantly delays ejaculation in a dose-dependent manner. KH-001 exhibits a fast onset of action, enabling a viable on-demand treatment for premature ejaculation, and represents a potential breakthrough in the treatment of a disease with a high unmet medical need. Kanna Health's President and inventor on the patent application, Dr Ryan Protzko, said "The data in our patent application show that KH-001 has tremendous potential as a treatment for premature ejaculation. The pharmacological profile of our compound is ideally suited to an acute, on-demand medication that treats premature ejaculation." To date, there are no approved treatments for premature ejaculation in the US. One of Kanna Health's scientific advisory board members, Dr. Andrea Burri, shared: "Premature ejaculation is a distressing condition, in which men orgasm too quickly before or during sexual intercourse. There are currently no treatments approved by the FDA, even though it affects up to 20% of men. These men report lower levels of sexual functioning and satisfaction, decreased self-esteem, and higher levels of personal distress. Partners of these men also suffer, and report sexual dissatisfaction and frustration, as well as problems in the relationship." John Boghossian, Kanna Health's CEO, stated: "We are really excited about this data and our development programme for KH-001. Based on the evidence we have to date, we believe KH-001 could represent a major breakthrough in the treatment of premature ejaculation. There is a major unmet medical need for a safe, efficacious on-demand treatment of premature ejaculation. We are advancing KH-001 into clinical development to address that need. This application complements the additional patent applications we have filed protecting KH-001." About Premature Ejaculation Premature ejaculation is the most common form of male sexual dysfunction (Carson & Gunn, IJIR, 18, S5-S13 (2006)). Men with premature ejaculation can feel stigmatised, and as a result, the true prevalence is likely to be higher than 20%. In addition to the physical symptoms, premature ejaculation frequently causes anxiety and emotional distress to affected individuals and often adversely impacts the relationship with their sexual partner. About Kanna Health Ltd Kanna Health is a preclinical-stage biopharmaceutical company. Kanna Health is developing novel medicines for areas of unmet medical need, derived from and inspired by the alkaloids found in Sceletium tortuosum (kanna). Kanna has been used for mood and performance enhancement purposes by the San and Khoikhoi communities in South Africa for hundreds of years. Further information: For further information, please contact John Boghossian, [email protected], +44 (0)7400 964226 SOURCE Kanna Health Ltd

100 项与 KH-001 相关的药物交易

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