A Two Part, Randomised, Double-blind, Placebo-controlled, Phase 2 Parallel Group Study to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 on Airway Responses Following Allergen Challenge in Subjects With Asthma (Part 1) and to Evaluate the Safety and Efficacy of Intravenously-Administered SelK2 in Subjects With Chronic Obstructive Pulmonary Disease (Part 2)

This study has two parts. The main purpose of Part 1 of this study will be to examine how safe and effective two doses of SelK2 is on participants with mild asthma. Lung function and inflammatory cell numbers will be measured in response to the administration of an allergen (a compound to which the participant is allergic) into the lungs in the presence or absence of SelK2. Part 2 of this study will examine how safe and effective one dose of SelK2 is on participants with chronic obstructive pulmonary disease (COPD). Lung function and inflammatory cell numbers will be measured in COPD patients in the presence or absence of SelK2. SelK2 may block the movement of key inflammatory cells into the lungs and consequently improve lung function in these two patient populations.

开始日期2020-08-18

申办/合作机构

Tetherex Pharmaceuticals Corp.初创企业

NCT03812328 / Completed临床2期

A Phase 2, Randomized, Active Comparator-Controlled, Open-Label, Adaptive Design Study to Assess the Safety and Efficacy of Intravenously-Administered SelK2 in Patients Undergoing Total Knee Arthroplasty

The main purpose of this study is to determine if an investigational medication called SelK2 works in preventing a condition called "venous thromboembolism" (VTE) in patients having a total knee replacement. SelK2 has been designed to attach to a protein found on blood cells and blood vessels. By attaching to this protein, SelK2 is designed to decrease the inflammatory process in the blood vessel wall that leads to the formation of blood clots in the vessel (called thrombosis). By decreasing the inflammatory process, SelK2 may reduce the risk of VTE following joint replacement surgery. In addition, because SelK2 is not a blood thinner, it is expected that the risk for bleeding will also be reduced.

开始日期2019-02-20

申办/合作机构

Tetherex Pharmaceuticals Corp.初创企业

100 项与 SelK-2 相关的临床结果

登录后查看更多信息

100 项与 SelK-2 相关的转化医学

登录后查看更多信息

100 项与 SelK-2 相关的专利（医药）

登录后查看更多信息

项与 SelK-2 相关的文献（医药）

2023-11-01·Acta pharmaceutica Sinica. B

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Article

作者: Li, Yuhan ; Ding, Longfei ; Yang, Zhiwei ; Xu, Jianqing ; Wu, Xianxian ; Zhang, Xu ; Yang, Yuhui ; Ding, Xiangqing ; Su, Jianrong ; Jiang, Xiaoliang ; Liu, Xing

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

2023-09-15·The Journal of clinical investigation

Hemolysis dictates monocyte differentiation via two distinct pathways in sickle cell disease vaso-occlusion.

Article

作者: Yazdanbakhsh, Karina ; Zhong, Hui ; Shayo, Sarah ; Dou, Kai ; Bao, Weili ; Shi, Patricia A ; Pal, Mouli ; Liu, Yunfeng ; Lobo, Cheryl A ; Campbell-Lee, Sally ; Su, Shan ; Aygun, Banu ; Mendelson, Avital ; An, Xiuli ; Manwani, Deepa

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by painful vaso-occlusive crises (VOC) and chronic hemolysis. The mononuclear phagocyte system is pivotal to SCD pathophysiology, but the mechanisms governing monocyte/macrophage differentiation remain unknown. This study examined the influence of hemolysis on circulating monocyte trajectories in SCD. We discovered that hemolysis stimulated CSF-1 production, partly by endothelial cells via Nrf2, promoting classical monocyte (CMo) differentiation into blood patrolling monocytes (PMo) in SCD mice. However, hemolysis also upregulated CCL-2 through IFN-I, inducing CMo transmigration and differentiation into tissue monocyte-derived macrophages. Blocking CMo transmigration by anti-P selectin antibody in SCD mice increased circulating PMo, corroborating that CMo-to-tissue macrophage differentiation occurs at the expense of CMo-to-blood PMo differentiation. We observed a positive correlation between plasma CSF-1/CCL-2 ratios and blood PMo levels in patients with SCD, underscoring the clinical significance of these two opposing factors in monocyte differentiation. Combined treatment with CSF-1 and anti-P selectin antibody more effectively increased PMo numbers and reduced stasis compared with single-agent therapies in SCD mice. Altogether, these data indicate that monocyte fates are regulated by the balance between two heme pathways, Nrf2/CSF-1 and IFN-I/CCL-2, and suggest that the CSF-1/CCL-2 ratio may present a diagnostic and therapeutic target in SCD.

2015-04-01·Arteriosclerosis, thrombosis, and vascular biology1区 · 医学

P-Selectin Inhibition Therapeutically Promotes Thrombus Resolution and Prevents Vein Wall Fibrosis Better Than Enoxaparin and an Inhibitor to von Willebrand Factor

1区 · 医学

Article

作者: Diaz, Jose A. ; Henke, Peter K. ; Wrobleski, Shirley K. ; Gabriel, Joy E. ; Alvarado, Christine M. ; Roelofs, Karen J. ; Schaub, Robert G. ; Lester, Patrick A. ; Lowe, Suzan E. ; Doornbos, Nichole K. ; Wakefield, Thomas W. ; Myers, Daniel D. ; Hawley, Angela E.

Objective—:

Aptamers are oligonucleotides targeting protein–protein interactions with pharmacokinetic profiles and activity reversal options. Although P-selectin and von Willebrand factor (vWF) have been implicated in the development of venous thrombosis (VT), no studies have directly compared aptamer efficacy with standard of care in VT. In this study, ARC5692, an anti-P-selectin aptamer, and ARC15105, an anti-vWF aptamer, were compared with low–molecular-weight heparin, enoxaparin, to test the efficacy of P-selectin or vWF inhibition in promoting thrombus resolution and preventing vein wall fibrosis, in a baboon model of VT.

Approach and Results—:

Groups were as follows: treatment arm: animals received P-selectin or vWF aptamer inhibitors or enoxaparin (n=3 per group). Controls received no treatment (n=3). Prophylactic arm: animals received P-selectin inhibitor (n=4) or vWF inhibitor (n=3). Treatment arm: P-selectin-inhibitor demonstrated a significant improvement in vein recanalization by magnetic resonance venography (73% at day 21), and significantly decreased vein wall collagen, compared with all groups. Anti–P-selectin equaled enoxaparin in maintaining valve competency by ultrasound. All control animals had compromised valve competency post thrombosis. Prophylactic arm: animals receiving P-selectin and vWF inhibitors demonstrated improved vein recanalization by magnetic resonance venography versus controls (80% and 85%, respectively, at day 21). Anti–P-selectin protected iliac valve function better than anti-vWF, and both improved valve function versus controls. No adverse bleeding events were observed.

Conclusions—:

The P-selectin inhibitor aptamer promoted iliac vein recanalization, preserved valve competency, and decreased vein wall fibrosis. The results of this work suggest that P-selectin inhibition maybe an ideal target in the treatment and prophylaxis of deep VT, warranting clinical trials.

项与 SelK-2 相关的新闻（医药）

2024-03-27

·Firstwordpharma

Pfizer sticks by timeline for sickle cell drug despite axing study over slow enrolment

Pfizer confirmed Wednesday that the termination of a Phase III study in the THRIVE programme for inclacumab will not affect its filing plans for the anti-P-selectin inhibitor in sickle cell disease. A spokesperson told FirstWord that a marketing submission to the FDA remains on track for 2026.A recent update on ClinicalTrials.gov indicated that Pfizer had ended the trial “due to poor accrual and associated recruitment challenges.” The entry noted that 72 patients with sickle cell disease and recurrent vaso-occlusive crises had been enrolled into the study, out of a target of approximately 280. The spokesperson said the trial was halted “due to slow recruitment,” although it has no read across to another late-stage study in the THRIVE programme. That trial is scheduled to read-out in August. Pfizer gained inclacumab through its purchase of Global Blood Therapeutics in 2022. The acquisition also included the HbS polymerisation inhibitor GBT601, now known as PF-07940367. That drug is being investigated in a Phase II/III study for sickle cell disease, with the spokesperson noting that termination of the inclacumab trial does not impact the former programme.

并购临床3期临床2期

2023-11-27

·GlobeNewswire-Health Care

AB Science: The clinical development of masitinib in sickle cell disease is among the 19 winning projects under the sixth call for “Hospital-Inuversity Research in health (RHU)”

PRESS RELEASE THE CLINICAL DEVELOPMENT OF MASITINIB IN SICKLE CELL DISEASE, A HIGHLY PREVALENT GENETIC CONDITION, IS AMONG THE 19 WINNING PROJECTS UNDER THE SIXTH CALL FOR "HOSPITAL-UNIVERSITY RESEARCH IN HEALTH (RHU)". THIS PROGRAM WILL FUND A MASITINIB PHASE 2 CLINICAL TRIAL AB SCIENCE WILL HOLD A WEBCAST ON THIS RESEARCH PROGRAM ON THURSDAY, NOVEMBER 30, 2023, FROM 3PM TO 4PM CET Paris, November 27, 2023, 8am CET AB Science SA (Euronext - FR0010557264 - AB) announces today that a new clinical development program for masitinib in sickle cell disease is among the 19 winning projects to be funded under the sixth call for "Hospital-University Research in Health" (Recherche Hospitalo-Universitaire en santé) projects, which is part of the Future Investments Program. The "Hospital-University Research in Health" (RHU) call for projects of the Future Investments Program, operated by the National Research Agency, aims to support innovative and large-scale research projects in the field of health. Focused on translational research, i.e., converting results in basic research into results that directly benefit humans, RHU projects involve academic, hospital, and business stakeholders. For this sixth wave, an international jury reviewed 62 applications based on criteria of scientific quality, innovation, and potential for medical and socio-economic impact. It proposed to select and fund 19 projects covering various therapeutic areas and medical needs. These 19 projects will receive an exceptional grant of 160 million euros from the Future Investments Program. As part of this call for projects, the SICKMAST project, funded with 9.2 million euros, aims to: First, identify and validate, from a database of 1500 patients (including 700 already identified), biomarkers highlighting the role of mast cells and basophils in orchestrating acute and chronic complications of sickle cell disease.Second, demonstrate in a phase 2 clinical trial the efficacy of masitinib in the treatment of acute and chronic complications of sickle cell disease in patients identified based on biomarkers. The Assistance Publique-Hôpitaux de Paris (AP-HP) will be the promoter of these phase 2 studies. AB Science will mainly be involved in supplying masitinib and monitoring masitinib pharmacovigilance data. AB Science remains free to carry out, as it sees fit, any potential phase 3 development following the success of phase 2. A new patent has been filed, which, if granted, will extend the international protection of masitinib in sickle cell disease until 2040. As part of the consortium agreement established for its patents, AB Science will pay royalties to APHP in the event of commercialization of masitinib in sickle cell disease. Prof. Olivier Hermine, Necker-Enfants malades AP-HP, coordinator of the SICKMAST program, said, "We are delighted to be among the laureates of this program, recognized for its extremely rigorous selection of innovative and medically impactful projects. Sickle cell disease represents a major public health challenge due to the number of affected individuals and the early mortality it causes. This program should allow us to demonstrate the relevance of selectively targeting two key immune cells in the treatment of this disease and identifying patients most likely to respond through new biomarkers." Alain Moussy, President and co-founder of AB Science, said, "We are very pleased with this collaboration with APHP, one of the largest promoters of clinical studies in France, whose research excellence is globally recognized. This project demonstrates the full potential of masitinib in targeting certain key immune cells involved in numerous pathologies. It opens an extremely promising new development avenue for masitinib and offers partnership prospects that we will explore to enable the registration and commercialization of masitinib in this indication under the best conditions." A webcast with experts in sickle cell disease will be held on November 30, 2023, to provide a more detailed presentation of this project. Login details for this live webcast will be provided later. Scientific rationale Inflammation mediated by innate immune cells and promoting vaso-occlusion has recently been shown to play a major role in sickle cell disease. In particular, our clinical observations and experimental work in mice, have revealed the involvement of mast cells and basophils in complications associated with sickle cell disease: The degree of mast cell activation in patients with sickle cell disease may contribute to the heterogeneity of inflammation and chronic and acute complications.The potential role of basophils in sickle cell disease has not been studied, however, given their role in various diseases and their ability to release substance P and histamine, they could also play important roles in the pathophysiology of sickle cell disease. Masitinib is an inhibitor of KIT, LYN, and FYN, three major kinases involved in the activation of mast cells and basophils. Epidemiology Sickle cell disease (SCD) is an autosomal recessive disorder affecting millions of people worldwide. Although life expectancy has increased over the last 20 years, acute and chronic complications still result in comorbidities, high social burden and premature death at around 40 years. Approximately 1.1% of couples worldwide are at risk of having a child with a hemoglobin disorder (sickle cell disease or thalassemia), and 2.3 conceptions per 1,000 are affected by sickle cell disease. Estimates suggest that each year, around 300,000 children are born with sickle cell disease, and this number could reach 400,000 by 2050 [1]. Sickle cell disease affects over 100,000 children and adults in the United States. In France, approximately 26,000 patients are affected (50% children, 50% adults). Medical need The classic view of sickle cell disease pathophysiology, involves polymerization of mutated hemoglobin (HbS) leading to red blood cell (RBC) sickling with subsequent hemolytic anemia, painful vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). Current treatment options such as hydroxycarbamide, chronic transfusion or anti-P-selectin antibodies, do not fully prevent life-threatening acute and chronic complications of sickle cell disease. Allogeneic stem cell transplantation and gene therapy are available only for a minority of patients, are associated with toxicity and are very expensive, which limits their use. There is a significant medical need to prevent the acute and chronic complications of sickle cell disease. Reference [1] Piel FB, Steinberg MH, Rees DC. Sickle Cell Disease. N Engl J Med. 2017;376(16):1561-1573. About AB ScienceFounded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment. AB Science has developed a proprietary portfolio of molecules and the Company’s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, inflammatory diseases and viral diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (ticker: AB). Further information is available on AB Science’s website: www.ab-science.com. Forward-looking Statements - AB ScienceThis press release contains forward-looking statements. These statements are not historical facts. These statements include projections and estimates as well as the assumptions on which they are based, statements based on projects, objectives, intentions and expectations regarding financial results, events, operations, future services, product development and their potential or future performance. These forward-looking statements can often be identified by the words "expect", "anticipate", "believe", "intend", "estimate" or "plan" as well as other similar terms. While AB Science believes these forward-looking statements are reasonable, investors are cautioned that these forward-looking statements are subject to numerous risks and uncertainties that are difficult to predict and generally beyond the control of AB Science and which may imply that results and actual events significantly differ from those expressed, induced or anticipated in the forward-looking information and statements. These risks and uncertainties include the uncertainties related to product development of the Company which may not be successful or to the marketing authorizations granted by competent authorities or, more generally, any factors that may affect marketing capacity of the products developed by AB Science, as well as those developed or identified in the public documents published by AB Science. AB Science disclaims any obligation or undertaking to update the forward-looking information and statements, subject to the applicable regulations, in particular articles 223-1 et seq. of the AMF General Regulations. For additional information, please contact: AB ScienceFinancial Communication & Media Relations investors@ab-science.com Attachment CP RHU VENG VF

临床2期引进/卖出

2023-01-23

·GlobeNewswire-Health Care

AltruBio Announces First Patient Dosed in Phase 1 Trial of Next-Generation Immune Checkpoint Enhancer ALTB-268 for the Treatment of Ulcerative Colitis

SAN FRANCISCO, Jan. 23, 2023 (GLOBE NEWSWIRE) -- AltruBio Inc. (“AltruBio” or “the Company”), a clinical stage biotech company dedicated to the development of novel therapeutics for the treatment of immunological diseases with high unmet medical needs, today announced that it has dosed the first patient in a Phase 1 study evaluating ALTB-268, its next-generation PSGL-1 antibody agonist serving as an immune checkpoint enhancer (ICE), in healthy volunteers. “The dosing of the first patient in this Phase 1 clinical trial represents a major milestone for AltruBio, and we look forward to executing on the clinical potential of ALTB-268, our next-generation, subcutaneously administered ICE,” said Judy Chou, Ph.D., President and Chief Executive Officer of AltruBio. “We are thrilled to bring ALTB-268 into the clinic to evaluate its safety and tolerability as a first step towards providing not only a more conveniently administered but potentially more durable and effective treatment option for patients suffering from immunological diseases including ulcerative colitis. The Phase 1 study was built on the clinically validated mechanism of action and strong preclinical data which showcased the improved potency in eliminating pathogenic chronic T cells. We believe ALTB-268 can realize the ‘pipeline-in-a-product’ potential for multiple autoimmune and inflammatory diseases in a patient population with high unmet medical needs.” The Phase 1 trial in healthy volunteers is a randomized, double-blind, single- and multiple- ascending dose study evaluating the safety, tolerability, pharmacokinetic/pharmacodynamic and immunogenicity of ALTB-268. About ALTB-268ALTB-268 is a next-generation PSGL-1 antibody agonist that acts as an immune checkpoint enhancer (ICE) that downregulates chronically activated T-cells by inhibiting the T-cell effector function, promoting T-cell exhaustion and apoptosis. PSGL-1 plays a key role in regulating late-stage, chronically activated T-cells. ALTB-268 helps to restore the immune system to a state of balance without interfering with cell migration. Its unique mechanism of action is the same as first-generation ICE, ALTB-168, which has previously obtained promising Phase 2a results in ulcerative colitis, psoriasis, psoriatic arthritis, and SR/TR-aGVHD. ALTB-268 can be administered subcutaneously and is potentially more potent than the company’s first-generation molecule. The Phase 1 study will examine the safety and tolerability in healthy volunteers with anticipated interim data in 1H 2023, with plans to follow with initiation of a Phase 2 study in ulcerative colitis. About AltruBio Inc.AltruBio is a privately held biotechnology company headquartered in San Francisco that is focused on developing novel therapeutics for the treatment of immunological diseases with high unmet medical needs. The company has leveraged its deep understanding of the role PSGL-1 plays as an immune checkpoint regulator protein to develop a platform for T-cell mediated immunological diseases. Its first-generation molecule, ALTB-168, a PSGL-1 agonist antibody serving as an immune checkpoint enhancer (ICE), has achieved proof of mechanism in four autoimmune and inflammatory diseases, including ulcerative colitis, steroid refractory acute graft-versus-host disease (SR-aGVHD), psoriatic arthritis, and psoriasis. The next-generation ICE, ALTB-268, is a tetravalent version of ALTB-168 and has demonstrated higher potency via the same mechanism, making it suitable for subcutaneous administration. ALTB-268 is now being evaluated in a Phase 1 clinical trial before advancing towards clinical studies in multiple autoimmune and inflammatory disorders. Note on Forward-Looking StatementsStatements made in this news release that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as expects, believes, intends, and similar expressions are intended to identify forward-looking statements. Actual results may differ materially from those projected in any forward-looking statement. Specifically, there are a number of important factors that could cause actual results to differ materially from those anticipated, such as the Company’s ability to raise additional capital, and risks related to the Company’s ability to initiate, and enroll patients in, planned clinical trials. You should not place undue reliance on any forward-looking statements. The Company assumes no obligation to update any forward-looking statements as a result of new information, future events or developments, except as required by law. Contacts AltruBio Inc: +1-415-655-6603 info@altrubio.com Media Contact:Luke ShiploLifeSci Communicationslshiplo@lifescicomms.com

临床1期临床结果免疫疗法临床2期AACR会议

100 项与 SelK-2 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床2期	英国	Tetherex Pharmaceuticals Corp.初创企业	2020-08-18
慢性阻塞性肺疾病	临床2期	英国	Tetherex Pharmaceuticals Corp.初创企业	2020-08-18
血栓形成	临床2期	保加利亚	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
血栓形成	临床2期	拉脱维亚	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
血栓形成	临床2期	立陶宛	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
血栓形成	临床2期	波兰	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
血栓形成	临床2期	乌克兰	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
静脉血栓栓塞	临床2期	保加利亚	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
静脉血栓栓塞	临床2期	拉脱维亚	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20
静脉血栓栓塞	临床2期	立陶宛	Tetherex Pharmaceuticals Corp.初创企业	2019-02-20

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03812328 (CTgov)	临床2期	血栓形成 \| 静脉血栓栓塞	207	SelK2 (SelK2)	憲壓壓壓艱衊蓋襯觸鹹(鬱鏇憲壓網窪衊網餘築) = 構觸選製獵衊鬱廠襯網範願餘鬱餘觸齋顧衊夢 (範壓餘繭鏇鹽廠淵鹽夢, 蓋構構膚繭醖獵夢膚遞 ~ 廠觸糧窪製範範選鹽鹹) 更多	-	2020-11-24
				SelK2+Enoxaparin (SelK2 and Enoxaparin)	憲壓壓壓艱衊蓋襯觸鹹(鬱鏇憲壓網窪衊網餘築) = 選襯餘膚鹹鹽淵繭憲鹽範願餘鬱餘觸齋顧衊夢 (範壓餘繭鏇鹽廠淵鹽夢, 製衊衊壓觸窪鑰選鏇網 ~ 膚簾築遞範廠衊鬱醖製) 更多