A Phase 1 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses and Multiple Ascending Doses of SION-451, and Multiple Dose Combinations of SION-451 and Complementary Modulators SION-2222 and SION-109 in Healthy Participants.

The purpose of Parts D and E of this Phase 1 study are to evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants.

开始日期2025-07-23

申办/合作机构

Sionna Therapeutics, Inc.

NCT05538585

/ Completed临床1期

A Food-Effect Study for the Safety and Assessment of Pharmacokinetics of Navocaftor and Galicaftor.

Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The objectives of this study are to assess the effect of food on the safety and pharmacokinetics of navocaftor and galicaftor.

开始日期2022-09-27

申办/合作机构

AbbVie, Inc.

NCT05530278

/ Completed临床1期

Assessment of Multiple-Dose Pharmacokinetics and Safety of the Co-administration of Galicaftor, Navocaftor and ABBV-576 and Potential of ABBV-576 for CYP3A Induction in Healthy Volunteers

Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The main objectives of this study are to assess the safety and pharmacokinetics of the combination therapy of galicaftor/navocaftor/ABBV-576.

开始日期2022-09-20

申办/合作机构

AbbVie, Inc.

100 项与 Galicaftor 相关的临床结果

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100 项与 Galicaftor 相关的转化医学

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100 项与 Galicaftor 相关的专利（医药）

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项与 Galicaftor 相关的文献（医药）

2024-03-01·European journal of pharmacology

PTI-801 (posenacaftor) shares a common mechanism with VX-445 (elexacaftor) to rescue p.Phe508del-CFTR

Article

作者: Miquéias Lopes-Pacheco ; Filipa C. Ferreira ; Mafalda Bacalhau ; Margarida D. Amaral

The deletion of a phenylalanine at position 508 (p.Phe508del) in the CFTR anion channel is the most prevalent variant in people with Cystic Fibrosis (CF). This variant impairs folding and stability of the CF transmembrane conductance regulator (CFTR) protein, resulting in its defective trafficking and premature degradation. Over the last years, therapeutic accomplishments have been attained in developing small molecules that partially correct p.Phe508del-CFTR defects; however, the mechanism of action (MoA) of these compounds has only started to be uncovered. In this study, we employed biochemical, fluorescence microscopy, and functional assays to examine the efficacy and properties of PTI-801, a newly developed p.Phe508del-CFTR corrector. To exploit its MoA, we assessed PTI-801 effects in combination with low temperature, genetic revertants of p.Phe508del-CFTR (the in cis p.Val510Asp, p.Gly550Glu, p.Arg1070Trp, and 4RK) and other correctors. Our results demonstrated that PTI-801 rescues p.Phe508del-CFTR processing, PM trafficking, and channel function (upon agonist stimulation) with greater correction effects in combination with ABBV-2222, FDL-169, VX-661, or VX-809, but not with VX-445. Although PTI-801 exhibited no potentiator activity on low temperature- and corrector-rescued p.Phe508del-CFTR, this compound displayed similar behavior to that of VX-445 on genetic revertants. Such evidence associated with the lack of additivity when PTI-801 and VX-445 were combined indicates that they share a common binding site to correct p.Phe508del-CFTR defects. Despite the high efficacy of PTI-801 in combination with ABBV-2222, FDL-169, VX-661, or VX-809, these dual corrector combinations only partially restored p.Phe508del-CFTR conformational stability, as shown by the lower half-life of the mutant protein compared to that of WT-CFTR. In summary, PTI-801 likely shares a common MoA with VX-445 in rescuing p.Phe508del-CFTR, thus being a feasible alternative for the development of novel corrector combinations with greater capacity to rescue mutant CFTR folding and stability.

2023-08-15·Biochemistry

Computational Exploration of Potential CFTR Binding Sites for Type I Corrector Drugs

Article

作者: Mitchell, Alexis ; Johnson, Quentin R. ; Evans, Claudia N. ; Girard, Christian ; Henager, Marissa E. ; Ramsdell, Havanna ; Lester, Anna ; Dixon, Brandon ; Poulos, Jack ; Reber, Callista ; Spinney, Allison ; Herring, Caitlin ; Sandman, Madeline ; Turlington, Mark

Cystic fibrosis (CF) is a recessive genetic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The recent development of a class of drugs called "correctors", which repair the structure and function of mutant CFTR, has greatly enhanced the life expectancy of CF patients. These correctors target the most common disease causing CFTR mutant F508del and are exemplified by the FDA-approved VX-809. While one binding site of VX-809 to CFTR was recently elucidated by cryo-electron microscopy, four additional binding sites have been proposed in the literature and it has been theorized that VX-809 and structurally similar correctors may engage multiple CFTR binding sites. To explore these five binding sites, ensemble docking was performed on wild-type CFTR and the F508del mutant using a large library of structurally similar corrector drugs, including VX-809 (lumacaftor), VX-661 (tezacaftor), ABBV-2222 (galicaftor), and a host of other structurally related molecules. For wild-type CFTR, we find that only one site, located in membrane spanning domain 1 (MSD1), binds favorably to our ligand library. While this MSD1 site also binds our ligand library for F508del-CFTR, the F508del mutation also opens a binding site in nucleotide binding domain 1 (NBD1), which enables strong binding of our ligand library to this site. This NBD1 site in F508del-CFTR exhibits the strongest overall binding affinity for our library of corrector drugs. This data may serve to better understand the structural changes induced by mutation of CFTR and how correctors bind to the protein. Additionally, it may aid in the design of new, more effective CFTR corrector drugs.

2021-10-13·Journal of biomolecular structure & dynamics

Identification of potential drugs against SARS-CoV-2 non-structural protein 1 (nsp1)

Article

作者: de Lima Menezes, Gabriela ; da Silva, Roosevelt Alves

Non-structural protein 1 (nsp1) is found in all Betacoronavirus genus, an important viral group that causes severe respiratory human diseases. This protein has significant role in pathogenesis and it is considered a probably major virulence factor. As it is absent in humans, it becomes an interesting target of study, especially when it comes to the rational search for drugs, since it increases the specificity of the target and reduces possible adverse effects that may be caused to the patient. Using approaches in silico we seek to study the behavior of nsp1 in solution to obtain its most stable conformation and find possible drugs with affinity to all of them. For this purpose, complete model of nsp1 of SARS-CoV-2 were predicted and its stability analyzed by molecular dynamics simulations in five different replicas. After main pocket validation using two control drugs and the main conformations of nsp1, molecular docking based on virtual screening were performed to identify novel potential inhibitors from DrugBank database. It has been found 16 molecules in common to all five nsp1 replica conformations. Three of them was ranked as the best compounds among them and showed better energy score than control molecules that have in vitro activity against nsp1 from SARS-CoV-2. The results pointed out here suggest new potential drugs for therapy to aid the rational drug search against COVID-19. Communicated by Ramaswamy H. Sarma.

项与 Galicaftor 相关的新闻（医药）

2026-09-16

·抗体圈

裁员46%、仅剩一条管线

当地时间9月16日，SEC一份文件把Sionna Therapeutics推至台前。这家总部位于马萨诸塞州的临床阶段生物企业，决定裁减约46%员工，将资源收拢至囊性纤维化（CF）联合疗法，同时拉长现金续航。 📢 药企PR、品牌负责人交流微信群已开启扫描上方群二维码加入药企PR交流社群，交流传播实操，共同探讨行业周期下的破局路径。伴随重组，高管层重新排兵：首席商务官Caroline Stark Beer本周二离职；首席医疗官Charlotte McKee额外接手研发，CFO Elena Ridloff兼任首席商务官，总法律顾问Jennifer Fitzpatrick增加项目管理职责，薪酬保持不变。精简架构，但不额外抬高人力成本。导火索并不复杂。核心资产SION-719的2a期试验未达主要终点。它原本定位为现有CF标准疗法的“附加项”，却在汗液氯化物这一关键指标上未取得统计学显著改善。公司随即终止该项目，并关停相关临床与生产合作合同。对临床阶段Biotech而言，数据失败不是普通挫折，而是战略分水岭：故事必须让位于现金。 Sionna的新赌注，是SION-451联合SION-2222的双药组合，代号AscenSION CF的2a期概念验证研究，预计2027年一季度启动。目前，它已是公司管线中唯一持续推进的在研项目。试验采用开放标签设计，招募F508del纯合突变成年CF患者；受试者停用Trikafta，直接转换为双联给药，周期28天，主要终点覆盖汗液氯化物、安全性和药代动力学。公司强调，裁员并非一刀切，参与该联合项目的人员将保留，以保障核心临床推进。与PreciSION CF不同，这次不再在Trikafta上“加药”，而是用双药直接替换Trikafta。好处是绕开NBD1稳定剂与依伐卡托之间的潜在相互作用，更干净地检验NBD1靶点假说；风险也直白：开放标签、短期给药、样本偏小，且设计逻辑部分来自事后回顾分析，尚缺前瞻性证据。它像一块早期路标，能指方向，却不能保证终点。 Sionna成立于2019年，创始团队来自赛诺菲（原健赞）深耕NBD1的科学家，并从赛诺菲获得NBD1稳定剂及相关CFTR调节剂的全球独家开发、商业化授权。 CF最常见突变F508del正发生在CFTR蛋白NBD1结构域，现有上市药无法直接稳定NBD1。 Sionna想做的，是用小分子NBD1稳定剂搭配CFTR矫正剂，修复蛋白功能，走出差异化路线。财务压力同样清晰。截至6月30日，公司累计赤字3.13亿美元；二季度末现金及有价证券2.683亿美元。本次重组预计产生约640万美元支出，主要是遣散与合同结算，大部分工作在2026年三季度落地，现金支付延续至四季度。董事会还批准员工期权重定价，设置18个月留存期。公司预计，降本后资金可支撑运营至2028年。这不是一家公司的孤立选择，而是海外罕见病Biotech的生存模板：临床失败后，快速裁员、收缩管线、保留核心项目，用现金换时间，等待下一组数据。 Sionna把未来压到AscenSION CF上。NBD1假说能否成立，最终不看叙事，而看2027年之后的人体数据。市场接下来盯的，也不只是裁员比例，而是这场“聚焦式求生”能否换来一张通往后期临床的门票。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

2026-09-16

·佰傲谷BioValley

裁员46%！重新挑战CF药物

在NBD1稳定剂SION-719的IIa期临床试验PreciSION CF失败后，Sionna Therapeutics的商业价值几乎一夜归零。现在，Sionna决定裁员47%，并在SION-719已经失败的基础上，再次推进另一款NBD1稳定剂的开发，再次挑战CF药物。首次挑战失败囊性纤维化（CF）的市场规模较大且增长潜力可观，一直以来CF市场都被Vertex所垄断。作为由赛诺菲-健赞拆分出来的Sionna，具有强劲的罕见病药物开发底蕴。同时，Sionna的首席医疗官Charlotte McKee博士曾是Vertex的CF药物临床开发副总裁，深度参与了多个重磅CF产品的开发。因此，Sionna一度被认为是Vertex的囊性纤维化药物帝国的挑战者。另外，不同于现有已获批的CF疗法，Sionna的核心药物SION-719是一种NBD1稳定剂，旨在与突变的NBD1结构域结合，稳定其结构，从而帮助整个CFTR蛋白正确折叠，从根本上恢复CFTR蛋白的正常功能。如果SION-719成功，将会改写CF市场的竞争格局。但是令人失望的是，SION-719在IIa期临床试验PreciSION CF中失败了，在“汗液氯化物水平变化”的核心终点上，SION-719联合疗法仅带来-1.0 mmol/L的安慰剂校正平均降幅，p值为0.7，在统计学上与安慰剂毫无区别。延伸阅读：Vertex挑战者败走这一重大失败也导致了Sionna当日股价暴跌超过90%。重新发起挑战尽管PreciSION CF失败了，但Sionna并没有完全放弃NBD1稳定剂这一药物机制。在最新的计划中，Sionna对PreciSION CF进行了事后分析，发现存在三个可能干扰治疗结果的因素，在排除混杂因素后，SION-719在经安慰剂校正后汗液氯化物水平平均减少量可达-8.6mmol/L，具有NBD1稳定的生物学活性。因此，Sionna将重点推进另一款NBD1稳定剂SION-451与SION-2222的双重组合方案。 SION-451是一款NBD1稳定剂；SION-2222是一款CFTR调节剂，通过靶向CFTR蛋白的TMD1区域，帮助CFTR蛋白正确折叠，从而恢复其功能。二者组合能够产生协同效应。根据披露，Sionna计划将在2027年第一季度启动SION-451+SION-2222的2期临床研究PreciSION CF，旨在F508del囊性纤维化纯合患者中评估SION-451+SION-2222的安全性和有效性。裁员46% 为了集中资源推进SION-451+SION-2222的开发，以及延长公司运营周期，Sionna将进行约46%的员工裁减，并实施其他节约成本措施。根据Sionna披露，在2026年第二季度收盘时，现金、现金等价物和可流通证券约为2.683亿美元。通过裁员、停止对SION-719的投资以及其他节约成本措施，预计现金流将持续到2029年下半年。同时，基于Sionna对PreciSION CF的事后分析，证明具有生物学活性时，Sionna的股价略有上涨。参考资料： 1.https://investors.sionnatx.com/news-releases/news-release-details/sionna-therapeutics-announces-plans-advance-sion-451-sion-2222

临床1期临床2期临床终止

2026-09-15

·FierceBiotech

Sionna lays off 46% of workforce in strategic shift after cystic fibrosis trial fail

Sionna Therapeutics is laying off almost half of its workforce as the company reels from the failure of its closely watched cystic fibrosis (CF) add-on program. A month ago, Sionna revealed that a small study of its NBD1 stabilizer SION-719 on top of Vertex Pharmaceuticals’ Trikafta wasn’t able to trigger a statistically significant reduction in sweat chloride among patients with CF homozygous for the F508del mutation. The failure seemed to put paid to Sionna’s most advanced attempt to challenge Vertex for the CF market. Investors drove Sionna’s stock down 90% in the aftermath of the readout, and the company has spent the following five weeks deciding on a path forward. Now, the biotech has opted to push ahead into a phase 2 study of another of its NBD1 stabilizers, dubbed SION-451, combined with its CFTR corrector SION-2222 for patients with CF homozygous for F508del. “It was important for us to take the time to complete a comprehensive post hoc data analysis to better understand the SION-719 PreciSION CF trial results and their potential implications before determining the right path forward for our dual combination,” Sionna CEO Mike Cloonan said in a Sept. 14 release. “The analysis identified important factors that we believe complicated interpretation of the trial and may have blunted the impact of NBD1 stabilization,” Cloonan added. “The post hoc findings, together with the favorable phase 1 results for SION-451 plus SION-2222, support advancing the dual combination into phase 2a.” This combo treatment already hinted at its potential last month when Sionna pitted the SION-451 and SION-2222 option against a combo of SION-451 and another CFTR corrector called SION-109. Target exposures exceeded the level Sionna set before the failed PreciSION CF readout, with SION-451 plus SION-2222 emerging as the preferred combination. To keep the resources flowing to this new strategy, Sionna is reducing its headcount by around 46%, including the departure of Chief Business Officer Caroline Stark Beer. The company oversaw 59 full-time employees at the start of the year. Sionna said it expects to “retain the core clinical, scientific, regulatory, technical and corporate capabilities required to advance the dual combination program.” The biotech ended June with $268.3 million in the bank, and said it expects the restructuring to cost around $6.4 million in the near-term while extending the company’s cash runway into the second half of 2029.

临床1期临床2期

100 项与 Galicaftor 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11724	-	-	DB14894

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
囊性纤维化	临床2期	澳大利亚	Lakefront Biotherapeutics	2017-01-01
囊性纤维化	临床2期	比利时	Lakefront Biotherapeutics	2017-01-01
囊性纤维化	临床2期	捷克	Lakefront Biotherapeutics	2017-01-01
囊性纤维化	临床2期	德国	Lakefront Biotherapeutics	2017-01-01
囊性纤维化	临床2期	爱尔兰	Lakefront Biotherapeutics	2017-01-01
囊性纤维化	临床2期	英国	Lakefront Biotherapeutics	2017-01-01

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临床结果

适应症

分期

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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


NCT04853368 (CTgov)	临床2期	囊性纤维化	48	ABBV-119+Navocaftor+Galicaftor (Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous)	繭醖齋壓鏇鑰鏇鹹構製(觸範夢蓋鑰膚鏇壓鑰衊) = 廠廠餘築鏇齋鹽齋網糧遞膚積範壓簾選蓋艱廠 (齋範觸餘糧艱構淵鹹遞, 3.68) 更多	-	2024-07-16
				ABBV-119+Navocaftor+Galicaftor (Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous)	繭醖齋壓鏇鑰鏇鹹構製(觸範夢蓋鑰膚鏇壓鑰衊) = 蓋網糧築糧觸鑰積鑰齋遞膚積範壓簾選蓋艱廠 (齋範觸餘糧艱構淵鹹遞, 5.62) 更多
NCT03969888 (CTgov)	临床2期	囊性纤维化	78	Placebo ABBV-2222+ABBV-3067 (ABBV-3067 50 mg + Placebo for ABBV-2222)	簾夢顧簾遞襯觸構鹽積(餘構鹽製壓憲積憲構選) = 製蓋夢顧願鏇積淵艱願觸選鑰夢窪鏇壓繭艱膚 (膚衊遞齋觸簾範夢醖憲, 齋顧襯選鹽衊糧淵膚廠 ~ 簾鑰壓遞獵顧觸製繭窪) 更多	-	2023-06-28
				Placebo ABBV-2222+ABBV-3067 (ABBV-3067 150 mg + Placebo for ABBV-2222)	簾夢顧簾遞襯觸構鹽積(餘構鹽製壓憲積憲構選) = 襯遞鏇願鑰製窪觸餘夢觸選鑰夢窪鏇壓繭艱膚 (膚衊遞齋觸簾範夢醖憲, 範鏇餘網夢構鏇蓋膚糧 ~ 醖蓋積廠積鹽鏇艱憲鏇) 更多
NCT03119649 (FLAMINGO, Pubmed \| J Cyst Fibros) 人工标引	临床2期	囊性纤维化	59	GLPG2222	簾築鹽廠襯窪鹽製積網(簾醖膚鑰淵鏇積壓鹽餘) = 選憲壓淵齋積願齋網築鬱鬱繭構製蓋淵廠襯壓 (夢積觸獵觸蓋糧網網鹽 )	不佳	2019-09-01
NCT03119649 (FLAMINGO, CTgov)	临床2期	囊性纤维化	59	Placebo+GLPG2222 100 mg (Cohort A: GLPG2222 100 mg QD)	鑰網鹹壓繭鹹願壓顧鹽 = 鹽鏇觸鑰膚鹽繭窪製觸壓鹹選鏇繭鬱觸艱製廠 (簾襯鹹憲觸願積衊願壓, 積觸糧製衊蓋鹽鹽鬱製 ~ 築顧糧艱艱淵獵糧憲鹽) 更多	-	2018-11-16
				Placebo+GLPG2222 200 mg (Cohort B: GLPG2222 200 mg QD)	鑰網鹹壓繭鹹願壓顧鹽 = 艱膚壓築襯艱夢觸鹹襯壓鹹選鏇繭鬱觸艱製廠 (簾襯鹹憲觸願積衊願壓, 鹽繭構蓋艱壓襯簾願鏇 ~ 鹽繭網鏇膚艱餘製廠製) 更多