更新于：2024-05-01

NLGase

β-葡萄糖苷酶2

更新于：2024-05-01

基本信息

别名

AD035、Beta-glucocerebrosidase 2、Beta-glucosidase 2

+ [19]

简介

Non-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) to free glucose and ceramides (such as N-acylsphing-4-enine) (PubMed:17105727, PubMed:30308956, PubMed:32144204). GlcCers are membrane glycosphingolipids that have a wide intracellular distribution (By similarity). They are the main precursors of more complex glycosphingolipids that play a role in cellular growth, differentiation, adhesion, signaling, cytoskeletal dynamics and membrane properties (By similarity). Involved in the transglucosylation of cholesterol, transfers glucose from GlcCer to cholesterol, thereby modifying its water solubility and biological properties (PubMed:32144204). Under specific conditions, may catalyze the reverse reaction, transferring glucose from cholesteryl-3-beta-D-glucoside to ceramide (such as N-acylsphing-4-enine) (Probable). May play a role in the metabolism of bile acids (PubMed:11489889, PubMed:9111029, PubMed:17080196). Able to hydrolyze bile acid 3-O-glucosides as well as to produce bile acid-glucose conjugates thanks to a bile acid glucosyl transferase activity (PubMed:11489889, PubMed:9111029, PubMed:17080196). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the galactosyl transfer between GalCers and cholesterol in vitro with lower activity compared with their activity against GlcCers (PubMed:32144204).

关联

项与 NLGase 相关的药物

BIA 28-6156

靶点

NLGase

作用机制

NLGase刺激剂

在研机构

National Institutes of Health [+1]

原研机构

Lysosomal Therapeutics, Inc.

在研适应症

帕金森病

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

AZ-3102

靶点

NLGase x UGCG

作用机制

NLGase抑制剂 [+1]

在研机构

Azafaros BV初创企业

原研机构

University of Leiden [+1]

在研适应症

GM2神经节苷脂贮积症 [+1]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

Sinbaglustat

靶点

NLGase x UGCG

作用机制

NLGase抑制剂 [+1]

在研机构

Idorsia Ltd.

原研机构

Idorsia Ltd.

在研适应症

溶酶体贮积病

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

项与 NLGase 相关的临床试验

NCT05758922 / Active, not recruiting临床2期

Randomized, Double Blind, Placebo Controlled, Multicenter, 12 Weeks Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AZ-3102 in Patients With GM2 Gangliosidosis or Niemann-Pick Type C Disease

This phase 2 is a randomized, double-blind, placebo controlled, 12 weeks study with daily oral administration of AZ-3102 aiming to evaluate the safety and pharmacokinetic (PK) profile in GM2 Gangliosidosis and Niemann-Pick type C disease (NP-C) patients. If approved by the country health authorities, a double-blind extension period will be proposed to the patients who complete the 12-week study.

开始日期2023-04-24

申办/合作机构

Azafaros BV初创企业

NCT05819359 / Recruiting临床2期

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in Subjects With Parkinson's Disease With a Pathogenic Variant in the Glucocerebrosidase (GBA1) Gene

The purpose of this randomized, double-blind, placebo-controlled study is to assess the efficacy of BIA 28-6156 over placebo in delaying clinical meaningful motor progression over 78 weeks in subjects with Parkinson's disease who have a pathogenic variant in the glucocerebrosidase 1 (GBA1) gene (GBA-PD).

开始日期2023-03-31

申办/合作机构

Bial R&d Investments SA

NCT05220072 / Completed临床1期

An Open Label, Single-dose, Single-period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of Carbon-14 BIA 28-6156 in Healthy Male Subjects

The study is designed to determine the absorption, distribution, metabolism and elimination (ADME) of BIA 28-6156 in humans, further explore the PK of BIA 28-6156, evaluate the extent of distribution of total radioactivity into blood cells, provide additional safety and tolerability information and collect samples for metabolite profiling and structural identification.

开始日期2021-08-28

申办/合作机构-

100 项与 NLGase 相关的临床结果

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100 项与 NLGase 相关的转化医学

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0 项与 NLGase 相关的专利（医药）

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4,814

项与 NLGase 相关的文献（医药）

2024-02-23·The journal of physical chemistry. B

Probing Activation and Conformational Dynamics of the Vesicle-Reconstituted β₂ Adrenergic Receptor at the Single-Molecule Level.

Article

作者: Marijonas Tutkus ; Christian V Lundgaard ; Salome Veshaguri ; Asger Tønnesen ; Nikos Hatzakis ; Søren G F Rasmussen ; Dimitrios Stamou

G-protein-coupled receptors (GPCRs) are structurally flexible membrane proteins that mediate a host of physiological responses to extracellular ligands like hormones and neurotransmitters. Fine features of their dynamic structural behavior are hypothesized to encode the functional plasticity seen in GPCR activity, where ligands with different efficacies can direct the same receptor toward different signaling phenotypes. Although the number of GPCR crystal structures is increasing, the receptors are characterized by complex and poorly understood conformational landscapes. Therefore, we employed a fluorescence microscopy assay to monitor conformational dynamics of single β₂ adrenergic receptors (β₂ARs). To increase the biological relevance of our findings, we decided not to reconstitute the receptor in detergent micelles but rather lipid membranes as proteoliposomes. The conformational dynamics were monitored by changes in the intensity of an environmentally sensitive boron-dipyrromethene (BODIPY 493/503) fluorophore conjugated to an endogenous cysteine (located at the cytoplasmic end of the sixth transmembrane helix of the receptor). Using total internal reflection fluorescence microscopy (TIRFM) and a single small unilamellar liposome assay that we previously developed, we followed the real-time dynamic properties of hundreds of single β₂ARs reconstituted in a native-like environment─lipid membranes. Our results showed that β₂AR-BODIPY fluctuates between several states of different intensity on a time scale of seconds, compared to BODIPY-lipid conjugates that show almost entirely stable fluorescence emission in the absence and presence of the full agonist BI-167107. Agonist stimulation changes the β₂AR dynamics, increasing the population of states with higher intensities and prolonging their durations, consistent with bulk experiments. The transition density plot demonstrates that β₂AR-BODIPY, in the absence of the full agonist, interconverts between states of low and moderate intensity, while the full agonist renders transitions between moderate and high-intensity states more probable. This redistribution is consistent with a mechanism of conformational selection and is a promising first step toward characterizing the conformational dynamics of GPCRs embedded in a lipid bilayer.

2024-02-20·Proceedings of the National Academy of Sciences of the United States of America

Structure and function of the Si3 insertion integrated into the trigger loop/helix of cyanobacterial RNA polymerase.

Article

作者: M Zuhaib Qayyum ; Masahiko Imashimizu ; Miron Leanca ; Rishi K Vishwakarma ; Amber Riaz-Bradley ; Yulia Yuzenkova ; Katsuhiko S Murakami

Cyanobacteria and evolutionarily related chloroplasts of algae and plants possess unique RNA polymerases (RNAPs) with characteristics that distinguish them from canonical bacterial RNAPs. The largest subunit of cyanobacterial RNAP (cyRNAP) is divided into two polypeptides, β'1 and β'2, and contains the largest known lineage-specific insertion domain, Si3, located in the middle of the trigger loop and spanning approximately half of the β'2 subunit. In this study, we present the X-ray crystal structure of Si3 and the cryo-EM structures of the cyRNAP transcription elongation complex plus the NusG factor with and without incoming nucleoside triphosphate (iNTP) bound at the active site. Si3 has a well-ordered and elongated shape that exceeds the length of the main body of cyRNAP, fits into cavities of cyRNAP in the absence of iNTP bound at the active site and shields the binding site of secondary channel-binding proteins such as Gre and DksA. A small transition from the trigger loop to the trigger helix upon iNTP binding results in a large swing motion of Si3; however, this transition does not affect the catalytic activity of cyRNAP due to its minimal contact with cyRNAP, NusG, or DNA. This study provides a structural framework for understanding the evolutionary significance of these features unique to cyRNAP and chloroplast RNAP and may provide insights into the molecular mechanism of transcription in specific environment of photosynthetic organisms and organelle.

2024-02-18·Micromachines

Biocatalytic Performance of β-Glucosidase Immobilized on 3D-Printed Single- and Multi-Channel Polylactic Acid Microreactors.

Article

作者: Andreas-Georgios Vasios ; Anastasia Skonta ; Michaela Patila ; Haralambos Stamatis

Microfluidic devices have attracted much attention in the current day owing to the unique advantages they provide. However, their application for industrial use is limited due to manufacturing limitations and high cost. Moreover, the scaling-up process of the microreactor has proven to be difficult. Three-dimensional (3D) printing technology is a promising solution for the above obstacles due to its ability to fabricate complex structures quickly and at a relatively low cost. Hence, combining the advantages of the microscale with 3D printing technology could enhance the applicability of microfluidic devices in the industrial sector. In the present work, a 3D-printed single-channel immobilized enzyme microreactor with a volume capacity of 30 μL was designed and created in one step via the fused deposition modeling (FDM) printing technique, using polylactic acid (PLA) as the printing material. The microreactor underwent surface modification with chitosan, and β-glucosidase from Thermotoga maritima was covalently immobilized. The immobilized biocatalyst retained almost 100% of its initial activity after incubation at different temperatures, while it could be effectively reused for up to 10 successful reaction cycles. Moreover, a multi-channel parallel microreactor incorporating 36 channels was developed, resulting in a significant increase in enzymatic productivity.

项与 NLGase 相关的新闻（医药）

2024-02-15

·药事纵横

FDA推迟Rocket罕见病基因疗法PDUFA日期

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。2024年2月13日，Rocket Pharmaceuticals宣布美国食品和药物管理局（FDA）已经延长了KRESLADI™（marnetegragene autotemcel）治疗严重白细胞粘附缺陷-I（LAD-I）的生物制品许可申请（BLA）的优先审查期。FDA 将审查期延长了三个月，至2024年6月30日，留出更多时间来审查 Rocket 为响应 FDA 信息请求而提交的化学、制造和控制 (CMC) 信息。FDA 进一步确认无需召开咨询委员会会议。William Blair分析师强调，延迟主要与FDA的人员配置问题有关，而不是申请本身。分析师指出，这已经不是第一次出现延迟三个月的情况，他们引用了Krystal Biotech公司的基因疗法 Vyjuvek。该疗法的 PDUFA 也被推迟了三个月，但最终还是获得了批准。该公司的股票 $RCKT 周二开盘后下跌了 4%，目前市值26亿美元。KRESLADI™基因疗法含有自体（患者）造血干细胞，这些干细胞已经用慢病毒载体进行了基因改造，传递ITGB2基因的功能副本，该基因编码β-2整合素成分CD18，促进白细胞粘附，并使其从血管进行外渗以抵抗感染的关键蛋白质。该项目在美国获得了FDA 的再生医学高级疗法 (RMAT)、罕见儿科和快速通道认证，在欧盟获得了 PRIME 和高级治疗药物产品 (ATMP) 认证，并在这两个地区获得了孤儿药认证。此次申请基于KRESLADI™全球1/2期研究的积极一线数据，结果显示所有9名随访期为12至24个月的LAD-I患者在输液后12个月（以及整个随访期间）的总存活率均为100%。数据还显示，与治疗前相比，重大感染的发生率大幅下降，同时有证据表明LAD-I相关皮肤病变得到了缓解，伤口修复能力得到了恢复。所有主要和次要终点均已达到，所有患者对 KRESLADI™ 的耐受性都非常好，没有发生与治疗相关的严重不良事件。Rocket Pharma 首席执行官、医学博士Gaurav Shah表示："我们期待着继续与FDA密切合作，共同承担起将 KRESLADI™等新型、具有潜在治疗效果的基因疗法带给最需要的患者所需的严格流程中的重大责任。我们有信心并专注于尽快为患者提供这种疗法。"Rocket 公司基于慢病毒（LV）载体的基因疗法主要针对血液病，包括针对范可尼贫血症（FA）的后期项目、白细胞粘附缺陷I型（LAD-I）的后期项目、以及丙酮酸激酶缺乏症 (PKD)的早期临床项目。基于腺相关病毒（AAV）的心血管产品组合包括针对达农病的晚期项目、针对 PKP2-致心律失常性心肌病（ACM）的早期临床试验项目、针对 BAG3 相关性扩张型心肌病（DCM）的临床前项目。公司管线参考资料：公司官网

基因疗法优先审批孤儿药快速通道

2024-02-07

·PRNewswire

Investigational targeted oral peptide JNJ-2113 demonstrated positive results in moderate-to-severe plaque psoriasis in Phase 2b study published in New England Journal of Medicine

Data from FRONTIER 1, a Phase 2b clinical trial, show JNJ-2113, the first and only targeted oral peptide that selectively blocks the IL-23 receptor, achieved the primary and all secondary endpoints including PASIa 100 and IGAb 0 responses of 40.5 percent and 45.2 percent, respectively SPRING HOUSE, Penn., Feb. 7, 2024 /PRNewswire/ -- Johnson & Johnson today announced publication in the New England Journal of Medicine (NEJM) of the Phase 2b FRONTIER 1 trial results for JNJ-2113.1 JNJ-2113 is the first and only investigational targeted oral peptide inhibitor designed to block the IL-23 receptor.2 IL-23 plays a critical role in pathogenic T-cell activation in moderate-to-severe plaque psoriasis (PsO) and underpins the inflammatory response in PsO and other dermatological and gastroenterological IL-23-mediated diseases.3,4 The FRONTIER 1 clinical trial achieved the primary and all secondary efficacy endpoints evaluating JNJ-2113 in adults with moderate-to-severe plaque PsO.1 The primary endpoint of the study was a reduction from baseline of at least 75 percent in the Psoriasis Area and Severity Index score (PASI 75 response) at Week 16. Study results demonstrated a significant dose-response on PASI 75 at Week 16 for adult patients who received JNJ-2113 compared to patients treated with placebo, with 79 percent of patients achieving a PASI 75 response in the highest dose group tested of 100 mg twice-daily. The data were consistent with the secondary endpoints, with patients who received the highest dose of JNJ-2113 achieving PASI 100 of 40.5 percent and IGA 0 (clear skin) of 45.2 percent.1 "The science behind advanced treatments for immune-mediated inflammatory diseases like PsO has advanced over the last few decades and patients desire treatment options that combine standard of care efficacy, an acceptable safety profile and flexible routes of administration," said Robert Bissonnette, M.D., Chief Executive Officer and Medical Director at Innovaderm Research, Montreal, Canada.d "The Phase 2b FRONTIER 1 data, as reported in NEJM, are very encouraging for the ongoing clinical development program and offer a reason to look forward to the continued research of investigational JNJ-2113 as an oral therapy that may offer an attractive and convenient treatment option for patients." Improvements were also consistent across Patient Reported Outcomes through Week 16.1 Patients who were treated with JNJ-2113 demonstrated greater improvements from baseline in the severity of their disease-related symptoms by Week 16, as assessed by the Psoriasis Symptoms and Signs Diary (PSSD)c.1 Among patients with baseline Dermatology Life Quality Index (DLQI)e scores greater than 1, significantly higher proportions of JNJ-2113-treated patients compared with placebo-treated patients achieved DLQI scores of 0/1 (no impact on quality of life) at Week 16.1 In this phase 2 study, rates of adverse events (AEs) were generally similar between the JNJ-2113 and placebo groups.1 The most common (≥5 percent of any treatment group) AEs were COVID-19 infection, nasopharyngitis, upper respiratory tract infection, diarrhea, headache, and cough.1 No relationship between the JNJ-2113 dose group and the occurrence of AEs or serious AEs was observed.1 Treatment with JNJ-2113 was also associated with lower serum levels of human beta-defensin 2 (hBD-2), relative to placebo, as early as Week 4.1 The lowest hBD-2 level was observed with the 100 mg twice-daily dose, beginning by Week 8.1 Lower levels of hBD-2 were observed with clinical response and indicate inhibition of the IL-17/IL-23 axis.5,6,7 "The impacts of living with moderate-to-severe plaque PsO are felt across all aspects of life and many patients do not seek advanced treatments because they have concerns with injectables and prefer an oral therapeutic option," said Lloyd Miller, M.D., Ph.D., Vice President, Immunodermatology Disease Area Leader, Johnson & Johnson. "We are encouraged by the study findings published in NEJM, including consistency across clinician and patient-reported outcomes and objective biomarkers. If approved, JNJ-2113 has the potential to improve both clinical and quality of life outcomes." The pivotal Phase 3 ICONIC clinical development program of JNJ-2113 in adult and adolescent patients with moderate-to-severe plaque PsO was initiated with two studies in Q4 2023 – ICONIC-LEAD and ICONIC-TOTAL – pursuant to the license and collaboration agreement between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc.8 ICONIC-LEAD is a randomized controlled trial (RCT) to evaluate the safety and efficacy of JNJ-2113 compared with placebo in participants with moderate-to-severe plaque PsO, with the higher efficacy bar of PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary endpoints.9 ICONIC-TOTAL is a RCT to evaluate the efficacy and safety of JNJ-2113 compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or palms of the hands and the soles of the feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.10 Other Phase 3 studies in the development program are expected to begin in Q1 2024, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will evaluate the safety and efficacy of JNJ-2113 compared with both placebo and deucravacitinib.11 The findings from the FRONTIER 1 clinical trial suggest the potential of JNJ-2113 across the spectrum of additional IL-23-mediated diseases.2,12 The Company has initiated the Phase 2b ANTHEM-UC study to evaluate the safety and effectiveness of JNJ-2113 compared with placebo in participants with moderately to severely active ulcerative colitis.12 Editor's Notes: a. The PASI score grades the amount of surface area on each body region that is covered by PsO plaques and the severity of plaque redness, thickness, and scaliness.13 b. The IGA is a five-point scale with a severity ranging from 0 to 4, where 0 indicates clear, 2 is mild, 3 is moderate, and 4 indicates severe disease.1 c. The PSSD is a patient-reported instrument that assesses severity of six symptoms (itch, skin tightness, burning, stinging, and pain) and five signs (dryness, cracking, scaling, shedding/flaking, redness, and bleeding) of PsO. An improvement (reduction) of 40 points or more is considered clinically meaningful.1 d. Dr. Robert Bissonnette is a paid consultant for Johnson & Johnson. He has not been compensated for any media work. e. The DLQI measures impact of any skin disease on daily life, and assesses symptoms, feelings, daily activities, leisure, work/school, relationships/sex, and treatment effects.14 About FRONTIER 1 (NCT05223868) The FRONTIER 1 Phase 2b trial (NCT05223868) is a randomized, multicenter, double-blind, placebo-controlled clinical trial that evaluated three once-daily dosages and two twice-daily dosages of JNJ-2113 taken orally.1,15 It was designed to assess the efficacy and safety of JNJ-2113 in patients with moderate-to-severe plaque PsO.1 A total of 255 participants were randomized into six treatment groups (placebo [n=43], 25 mg daily [n=43], 25 mg twice-daily [n=41], 50 mg daily [n=43], 100 mg daily [n=43], and 100 mg twice-daily [n=42]).1 The total duration of the trial was up to 24 weeks, which included a four-week screening period, a 16-week treatment period and a four-week safety follow-up period.1 The primary endpoint of the clinical trial was the proportion of patients achieving PASI 75 at 16 weeks.1 Secondary endpoints at Week 16 included change from baseline in PASI total score, proportion of participants achieving PASI 90 and PASI 100 score, proportion of participants achieving an Investigator's Global Assessment (IGA) score of cleared (0) or minimal (1), change from baseline in Body Surface Area (BSA), change from baseline in Psoriasis Symptoms and Signs Diary (PSSD) symptoms scores, percentage of participants achieving PSSD symptoms score=0 among participants with a baseline symptom score ≥1, proportion of participants achieving a Dermatology Life Quality Index (DLQI) of 0 or 1 among participants with baseline DLQI Score >1, change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS-29) domain score, proportion of participants who achieve ≥ 5-point improvement from baseline in PROMIS-29 domain score, and number of participants with adverse events and serious adverse events up to 24 weeks.15 About Plaque Psoriasis (PsO) Plaque PsO is an immune-mediated disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful.16 It is estimated that eight million Americans and more than 125 million people worldwide live with the disease.17 Nearly one-quarter of all people with PsO have cases that are considered moderate-to-severe.17 Living with PsO can be a challenge and impact life beyond a person's physical health, including emotional health, relationships, and handling the stressors of life.18 About JNJ-77242113 (JNJ-2113) JNJ-2113 was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist Therapeutics and Johnson & Johnson. Johnson & Johnson retains exclusive worldwide rights to develop JNJ-2113 in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.19, 20, 21 Investigational JNJ-2113 is the first targeted oral peptide designed to block the IL-23 receptor,2 which underpins the inflammatory response in moderate-to-severe plaque PsO and other IL-23-mediated diseases.3,4 JNJ-2113 binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells.22 The license and collaboration agreement established between Protagonist and Janssen Biotech, Inc., in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to JNJ-2113.23 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC is a Johnson & Johnson Company. Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding JNJ-2113. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. Neither Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. © Johnson & Johnson, Inc. 2024. All rights reserved. Bissonnette R, et al. An oral interleukin-23–receptor antagonist peptide for plaque psoriasis. N Engl J Med. 2024;390:510-21. DOI: 10.1056/NEJMoa2308713. Bissonnette R, et al. Data presentation. A phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER 1. Presented at WCD 2023, July 3-8. Razawy W, et al. The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling. Eur J Immunol. 2018 Feb; 48(2): 220–229. Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112–124. Kolbinger F, et al. β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with psoriasis. J Allergy Clin Immunol 2017;139:923-32. Morita A, et al. Assessment of serum biomarkers in patients with plaque psoriasis on secukinumab. J Dermatol 2020;47:452-7. Jansen PA, et al. β-Defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin. PLoS One. 2009 Mar; 4(3): e4725. doi: 10.1371/journal.pone.0004725. PMID: 19266104; PMCID: PMC2649503. Protagonist Therapeutics. Press release. Protagonist announces advancement of JNJ-2113 across multiple indications. Available at: . Accessed February 2024. Clinicaltrials.gov. A study of JNJ-2113 in adolescent and adult participants with moderate-to-severe plaque psoriasis (ICONIC-LEAD). Identifier NCT06095115. . Accessed January 2024. Clinicaltrials.gov. A study of JNJ-2113 for the treatment of participants with plaque psoriasis involving special areas (scalp, genital, and/or palms of the hands and the soles of the feet) (ICONIC-TOTAL). Identifier NCT06095102. . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist announces two new phase 3 ICONIC studies in psoriasis evaluating JNJ-2113 in head-to-head comparisons with deucravacitinib. Available at: . Accessed February 2024. Clinicaltrials.gov. A study of JNJ-2113 in participants with moderately-to-severely active ulcerative colitis (ANTHEM-UC). Identifier NCT06049017. . Accessed January 2024. Thompson Jr, D. How the Psoriasis Area and Severity Index works. Everyday Health. Available at: . Accessed January 2024. Finlay AY, et al. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210-6. doi: 10.1111/j.1365-2230.1994.tb01167.x. PMID: 8033378. Clinicaltrials.gov. A study of JNJ-2113 in participants with moderate-to-severe plaque psoriasis (FRONTIER 1). Identifier NCT05223868. . Accessed January 2024.EU Clinical Trials Register. A study of JNJ-2113 in participants with moderate-to-severe plaque psoriasis (FRONTIER 1). EudraCT 2021-003700-41. . Accessed January 2024. National Psoriasis Foundation. About psoriasis. Available at: . Accessed January 2024. National Psoriasis Foundation. Psoriasis statistics. Available at: . Accessed January 2024. National Psoriasis Foundation. Life with psoriasis. Available at: . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist Therapeutics announces amendment of agreement with Janssen Biotech for the continued development and commercialization of IL-23 antagonists. Available at: . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist Reports positive results from Phase 1 and pre-clinical studies of oral Interleukin-23 receptor antagonist JNJ-2113. Available at: . Accessed January 2024. Protagonist Therapeutics. Press release. Protagonist Therapeutics announces positive topline results for Phase 2b FRONTIER 1 clinical trial of oral IL-23 receptor antagonist JNJ-2113 (PN-235) in psoriasis. Available at: . Accessed January 2024. Pinter A, et al. Data Presentation. JNJ-77242113 Treatment Induces a Strong Systemic Pharmacodynamic Response Versus Placebo in Serum Samples of Patients with Plaque Psoriasis: Results from the Phase 2, FRONTIER 1 Study. Presented at EADV 2023, October 11-14. Johnson & Johnson. Press release. Janssen enters into worldwide exclusive license and collaboration agreement with Protagonist Therapeutics, Inc. for the oral Interlukin-23 receptor antagonist drug candidate for the treatment of Inflammatory Bowel Disease. Available at: . Accessed January 2024. SOURCE Johnson & Johnson

临床2期临床结果引进/卖出临床3期临床1期

2022-07-23

·凯莱英药闻

2022年6月医药交易汇总

欢迎关注凯莱英药闻2022年6月，全球共产生57起交易，其中首付款超过16亿，总交易高达116亿美元。在项目类型上，其中创新药项目40个，技术类16个，生物仿制药4个，微创新项目2个。在疾病划分领域，其中肿瘤领域项目高达25个，罕见病领域8个，神经领域7个，血液领域6个，免疫领域5个，皮肤和泌尿生殖领域各4个，感染和眼科领域3个，骨骼领域2个，呼吸、心血管和消化领域各1个。在交易数量上，其中强生（3）、赛诺菲（2）、安斯泰来（2）作为受让方，和铂医药（2）、艾博生物（2）作为转让方，产生的交易最多。在总交易金额上，排名前5的交易依次是：诺华和Precision（14.75亿）、安斯泰来和 Sutro（13.57亿）、罗氏和Repare（13.25亿）、再生元和赛诺菲（11.00亿）、Menarini和NewAmsterdam（10.95亿）。- 医药交易汇总 -- 重点交易介绍 -1、诺华与Precision 合作开发体内基因编辑，用于治疗包括镰状细胞病在内的疾病。2022年6月21日，Precision BioSciences宣布与 Novartis Pharma签订全球独家体内基因编辑研发合作和许可协议，合作将 Precision 专有的 ARCUS 基因组编辑平台和基因插入能力与诺华的药物发现和基因治疗专业知识相结合。作为协议的一部分，Precision 将开发一种定制的 ARCUS 核酸酶，进行体内基因编辑，用于治疗包括镰状细胞病和β地中海贫血等血红蛋白病。诺华将负责所有后续研究的开发、制造和商业化活动。Precision将收到 7500 万美元的预付款，并有资格获得总计约 14 亿美元的里程碑付款，以及产品销售的分层特许权使用费。2、Astellas 和 Sutro 共同开发新型免疫刺激抗体药物偶联物 (iADCs)2022年6月28日，Astellas Pharma与Sutro Biopharma共同宣布，双方达成一项全球战略合作和许可协议，共同开发新型免疫刺激抗体药物偶联物 (iADC)。此次合作将充分利用 Astellas 和 Sutro 双方在药物领域优势，加速针对 iADC的三个靶点药物的开发和研究工作；Sutro 依据自身技术平台筛选和确定候选化合物，Astellas 将进行临床开发和商业化生产。根据协议条款，Sutro 将收到 9000 万美元的现金预付款，用于开发三个iADC，并有资格为每个候选化合物获得高达4.225亿美元的开发、监管和商业里程碑，以及分级特许权使用费。Sutro有权选择与Astellas在美国地区共同承担某候选化合物在商业化开发阶段的相关成本与利润；倘若Sutro对某一特定的候选化合物行使这一选择权，Astellas和Sutro亦将共同分担在美国开发和商业化的利润/亏损。3、罗氏与Repare就 Camonsertib开发达成全球许可和合作协议2022年6月1日，Repare Therapeutics宣布与与罗氏就开发和商业化 camonsertib（也称为 RP-3500）达成全球许可和合作协议，这是一种 ATR（共济失调-毛细血管扩张症突变基因Rad3 相关蛋白激酶）的强效和选择性口服小分子抑制剂，用于治疗具有特定合成致死基因组改变，包括 ATM（共济失调-毛细血管扩张突变）基因改变的肿瘤。根据协议内容，Repare 将收到 1.25 亿美元的预付款，并有资格获得额外高达 12 亿美元的潜在开发、监管、商业和销售里程碑，以及全球净产品销售的特许权使用费；罗氏将承担 camonsertib 的开发，并有可能将开发扩展到其他肿瘤和多种组合研究中。4、Menarini与NewAmsterdam就CETP抑制剂obicetrapib签署独家许可协议美纳里尼（Menarini）与NewAmsterdam就开发拟用于治疗心血管疾病的CETP抑制剂候选药物obicetrapib签署独家许可协议，美纳里尼将获得obicetrapib在欧洲上市后的商业化授权。根据协议，NewAmsterdam将获得1.15亿欧元的预付款和2750万欧元的研发资金，最高8.63亿欧元的潜在里程碑付款，以及产品在欧洲的销售分成。Obicetrapib 是新一代口服、低剂量、每日一次的胆固醇酯转移蛋白（CETP）抑制剂候选药物，作为最大限度耐受他汀的一种降低低密度脂蛋白（LDL）的辅助药物，该药具有良好的安全性和有效性。5、礼来就Kv1.3靶向治疗药物与DESRES达成全球独家许可协议2022年6月13日，D. E. Shaw Research (DESRES)宣布，已与礼来就Kv1.3靶向治疗药物达成全球独家许可协议。根据协议条款，礼来获得Kv1.3靶向治疗药物（包括DES-7114）在全球的临床开发和商业化权利，并向DESRES支付6000万美元的首付款、4.75亿美元里程付款和销售分成。DES-7114是一款高选择性离子通道蛋白Kv1.3口服小分子抑制剂，是基于DESRES开发构建的专用超级计算机实现的，目前已在几种慢性炎症和自身免疫性疾病的临床前模型中证明了疗效，包括溃疡性结肠炎、克罗恩病和特应性皮炎。6、复宏汉霖就两款单抗生物药与Organon达成授权合作2022年6月13日，复宏汉霖宣布与Organon公司签署授权许可及供货协议，授予其对公司自主开发的帕妥珠单抗生物类似药HLX11（重组抗HER2结构域II人源化单克隆抗体注射液）、地舒单抗生物类似药HLX14（重组抗RANKL全人单克隆抗体注射液）两款产品在除中国以外全球范围内进行独家商业化的权益。根据协议条款，复宏汉霖将从交易中获得5.41亿美元的潜在收入，其中7300万美元为交易首付款。Organon还可以选择就复宏汉霖自主开发的伊匹木单抗生物类似药HLX13的全球商业化独家权利进行谈判。7、Biogen引进Alectos的GBA2抑制剂AL018112022年6月6日，Biogen和Alectos Therapeutics已签订许可和合作协议，以开发和商业化一种新的临床前选择性GBA2抑制剂AL01811。AL01811是一款具有first-in-class的潜力，可作为帕金森病 (PD) 患者的疾病改善口服治疗。此次合作将 Alectos在小分子治疗方面的专业知识与Biogen在运动障碍方面的开发能力相结合。根据协议条款，Biogen将支付1500万美元的预付款，以获得AL01811和其他未命名的备用分子的全球独家许可；此外，如果合作达到某些里程碑，Alectos有资格获得高达7750万美元的潜在开发付款和6.3亿美元的潜在商业里程碑付款，以及销售分成。8、默克与Proxygen签订分子胶战略性合作与许可协议2022年6月2日，生物科技公司Proxygen宣布与德国默克签订一项战略性合作与许可协议。这一合作将为Proxygen带来最高4.95亿欧元（5.54亿美元）的研发资金、多种里程碑付款和特许权使用费。根据协议内容，双方将共同开发分子胶并将产品推入临床。Proxygen开发了一种高度通用的分子胶降解剂发现引擎，有望改变分子胶类药物的发现过程，促进分子胶的发展，这种不依赖蛋白酶的筛选方法可以针对难以靶向或不可成药的靶标，进行大规模特异性地鉴定分子胶降解剂。9、嘉和生物与艾博生物合作开发肿瘤mRNA药物2022年6月24日，嘉和生物与艾博生物共同宣布，已经于近期达成合作开发协议，共同开发具有全球创新性的mRNA产品以及相关药品。双方将基于嘉和生物抗体开发平台，与艾博生物旗下mRNA技术平台结合，进行肿瘤治疗的mRNA药物的探索研究。嘉和生物已经成功搭建早期发现全球首创/全球最佳、差异化、免疫肿瘤双/多特异性抗体研发平台，目前已有数个FIC/BIC潜力的双/多抗分子发现项目启动。艾博生物在中国mRNA领域处领先地位，凭借自主创新的mRNA技术平台扩充旗下疫苗产品管线的同时，丰富现有的肿瘤治疗领域管线，并扩展到更多治疗领域。10、多禧生物宣布与杨森就新型抗体偶联药物（ADC）达成合作和许可协议6月1日，杭州多禧生物宣布与强生公司旗下杨森制药达成合作和许可协议。根据协议，多禧生物将应用其独有的ADC创新平台与杨森所提供的独有抗体，双方将就至多5个靶点开发新型ADC药物。强生创新协助促成该合作协议，强生创新旗下投资公司-JJDC也对多禧生物进行了股权投资。多禧生物目前拥有20条处于不同研究阶段的ADC管线，其中5款ADC药物已经处于临床开发阶段。2021年3月，多禧生物完成了由高瓴创投、晨岭资本和CPE领投的C轮融资。感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618"。

合作抗体免疫疗法小分子药物信使RNA