A Phase 1/2 Trial of Direct Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human Vascular Endothelial Growth Factor, to the Ischemic Myocardium of Subjects with Angina Pectoris Secondary to Coronary Artery Disease that is Refractory to Drug Therapy and Unsuitable for Revascularization

开始日期2022-01-20

申办/合作机构

Xylocor Therapeutics, Inc.

NCT01757223 / Withdrawn临床1/2期IIT

Phase I/II Study, Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human Vascular Endothelial Growth Factor to the Ischemic Myocardium...

The proposed Phase I/II clinical trial will be used to determine the safety and toxicity of direct administration of the vector AdVEGF-All6A+ to the ischemic myocardium and to generate preliminary evidence regarding whether direct administration of AdVEGF-All6A+ to the ischemic myocardium will induce growth of collateral blood vessels and improve cardiac function. This is a three-part, multinational/multi-center, placebo controlled study.

开始日期2020-12-01

申办/合作机构

Weill Medical College of Cornell University

NCT04125732 / Completed临床1/2期

A Phase 1/2 Trial of Direct Administration of AdVEGF-All6A+, a Replication Deficient Adenovirus Vector Expressing a cDNA/Genomic Hybrid of Human VEGF, to the Ischemic Myocardium of Subjects With Angina Pectoris

The primary purpose of this trial is to determine the safety of XC001 (AdVEGFXC1) in patients who suffer from angina caused by coronary artery disease and have no other treatment options. Subjects in this study will receive one of four intramyocardial doses of XC001 that expresses human vascular endothelial growth factor (VEGF) which induces therapeutic angiogenesis (revascularization).

开始日期2020-01-24

申办/合作机构

Xylocor Therapeutics, Inc.

100 项与 Encoberminogene Rezmadenovec 相关的临床结果

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100 项与 Encoberminogene Rezmadenovec 相关的转化医学

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100 项与 Encoberminogene Rezmadenovec 相关的专利（医药）

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项与 Encoberminogene Rezmadenovec 相关的文献（医药）

2024-01-01·Gene therapy

Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases

Article

作者: Dittrich, Howard C ; Gianchetti, Albert ; Thorne, Barb ; Stewart, Duncan J ; Manza, Linda L ; Reinhardt, Rickey R ; Byrnes, Dawn

Adenovirus-mediated gene therapy holds promise for the treatment of cardiovascular diseases such as refractory angina. However, potential concerns around immunogenicity and vector dissemination from the target injected tissue require evaluation. This study was undertaken to evaluate the safety and biodistribution of XC001, a replication-deficient adenovirus serotype 5 vector expressing multiple isoforms of human vascular endothelial growth factor (VEGF), following direct administration into normal rat myocardium. Animals received the buffer formulation or increasing doses of XC001 (1 × 10⁷, 2.5 × 10⁸ or 2.5 × 10⁹ viral particles). Based on in-life parameters (general health, body weights, clinical pathology, serum cardiac troponin I, plasma VEGF, and gross necropsy), there were no findings of clinical concern. On Day 8, intramyocardial administration of XC001 was associated with dose-related, left ventricular myocardial inflammation at injection sites, resolving by Day 30. XC001 DNA was not detected in blood at any time but was present at Day 8 around the site of injection and to a much lesser extent in the spleen, liver, and lungs, persisting at low levels in the heart and spleen until at least Day 91. These findings demonstrate that intramyocardial injection of XC001 is supported for use in human studies.

2023-08-01·Circulation. Cardiovascular interventions

EXACT Trial: Results of the Phase 1 Dose-Escalation Study.

Article

作者: Henry, Timothy D ; Sun, Benjamin C ; Dittrich, Howard C ; Latter, David A ; Crystal, Ronald G ; Tarka, Elizabeth A ; Byrnes, Dawn ; Ohman, E Magnus ; Povsic, Thomas J ; Arnaoutakis, George J ; Peterson, Mark W ; Williams, Adam R ; Rosengart, Todd K ; Traverse, Jay H ; Mokadam, Nahush A ; DiCarli, Marcelo F ; Answini, Geoffrey A ; Boudoulas, Konstantinos D ; Anderson, R David ; Pepine, Carl J

BACKGROUND:

New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenesis in preclinical models; however, the maximal tolerated dose and safety of direct epicardial administration remain unknown.

METHODS:

In the phase 1 portion of this multicenter, open-label, single-arm, dose-escalation study, patients with refractory angina received increasing doses of encoberminogene rezmadenovec (1×10⁹, 1×10¹⁰, 4×10¹⁰, and 1×10¹¹ viral particles) to evaluate its safety, tolerability, and preliminary efficacy. Patients had class II to IV angina on maximally tolerated medical therapy, demonstrable ischemia on stress testing, and were angina-limited on exercise treadmill testing. Patients underwent minithoracotomy with epicardial delivery of 15 0.1-mL injections of encoberminogene rezmadenovec. The primary outcome was safety via adverse event monitoring over 6 months. Efficacy assessments included difference from baseline to months 3, 6 (primary), and 12 in total exercise duration, myocardial perfusion deficit using positron emission tomography, angina class, angina frequency, and quality of life.

RESULTS:

From June 2, 2020 to June 25, 2021, 12 patients were enrolled into 4 dosing cohorts with 1×10¹¹ viral particle as the highest planned dose. Seventeen serious adverse events were reported in 7 patients; none were related to study drug. Six serious adverse events in 4 patients were related to the thoracotomy, 3 non-serious adverse events were possibly related to study drug. The 2 lowest doses did not demonstrate improvements in total exercise duration, myocardial perfusion deficit, or angina frequency; however, there appeared to be improvements in all parameters with the 2 higher doses.

CONCLUSIONS:

Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1×10¹¹ viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1×10¹¹ viral particle) was carried forward into phase 2.

REGISTRATION:

URL: https://www.

CLINICALTRIALS:

gov; Unique identifier: NCT04125732.

2021-11-01·American heart journal2区 · 医学

Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations

2区 · 医学

Article

作者: Henry, Timothy D ; Answini, Geoffrey A ; Pepine, Carl J ; Ohman, E Magnus ; Crystal, Ronald G ; Mokadam, Nahush A ; Dittrich, Howard C ; Rosengart, Todd K ; Traverse, Jay H ; Povsic, Thomas J ; Reinhardt, Rickey R

BACKGROUND:

Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect.

METHODS:

The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1 × 10⁹, 1 × 10¹⁰, 4 × 10¹⁰, and 1 × 10¹¹ viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency.

CONCLUSIONS:

The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation.

CLINICAL TRIAL REGISTRATION:

NCT04125732.

项与 Encoberminogene Rezmadenovec 相关的新闻（医药）

2024-05-02

·BioSpace

XyloCor Therapeutics Positive EXACT Phase 2 Data for Lead Candidate XC001 Simultaneously Presented at Society for Cardiovascular Angiography & Interventions (SCAI) 2024 Scientific Sessions

– Positive Phase 2 EXACT Trial results validate transformative potential of novel gene therapy XC001 for treatment of refractory angina and support continued clinical development – Novel therapeutic approach aims to fill significant unmet medical need for patients with refractory angina who have exhausted available treatment options and have a debilitating quality-of-life WAYNE, Pa.--(BUSINESS WIRE)-- XyloCor Therapeutics, Inc., a clinical‑stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today presented final results from the Phase 2 portion of its Phase 1/2 clinical trial (EXACT) of its lead gene therapy candidate XC001 (encoberminogene rezmadenovec) for refractory angina at the Society for Cardiovascular Angiography & Interventions (SCAI) 2024 Scientific Sessions, May 2-4, 2024 in Long Beach, CA. These encouraging results supporting XC001’s safety and efficacy potential are being simultaneously published in Circulation: Cardiovascular Interventions. The EXACT trial assessed the use of one-time gene therapy with XC001 as a new therapeutic approach in refractory angina – a debilitating and chronic condition that impacts over one million people in the United States and is growing in prevalence. XC001 is designed to reduce ischemic burden by creating new blood vessels in the heart through the local expression of multiple vascular endothelial growth factor (VEGF) isoforms. In the Phase 2 portion of the EXACT trial, 32 patients with class II-IV angina were dosed with the maximal dose of XC001 through minimally-invasive transepicardial delivery (direct administration to the heart). “The results of the EXACT trial suggest that angiogenic gene therapy with XC001 has the potential to improve cardiovascular outcomes for refractory angina patients without revascularization or other treatment options,” said Thomas Povsic, M.D., Ph.D., Professor of Medicine, Duke University School of Medicine and Kenta Nakamura, M.D., Assistant Professor at the University of Washington, lead authors of the EXACT study results. “There is significant need for novel therapies for this serious and disabling condition and we hope that the clinically meaningful evidence emerging from the EXACT trial is the catalyst for continued development that will further validate the potential of this innovative gene therapy for patients.” The Phase 2 results validated the transformative disease modifying potential of XC001 to reduce ischemia and improve the quality-of-life for cardiac patients who have no treatment options. The results demonstrated that treatment with XC001 can be safely administered and achieve durable clinical improvements including: increases in exercise duration, decrease in ischemic burden as measured by Positron Emission Tomography (PET) imaging, and a reduction in angina frequency. Notably, 93% of patients in the trial entered the trial with chest paint so severe that it markedly limited daily activities and six months after treatment 43% of patients had no chest pain with ordinary activities. VEGF gene therapy with XC001 was well tolerated in the patient population and there were no serious adverse events related to the drug or unexpected serious adverse events related to XC001 administration. “The results from the EXACT trial represent a promising moment for people with refractory angina and the cardiovascular community as we drive forward toward our goal to deliver a long overdue new treatment option,” said Al Gianchetti, President and CEO of XyloCor. “We are preparing our next clinical trial to advance the development of XC001 and further unlock its transformative medical potential for patients and their families.” Details regarding the SCAI 2024 scientific session is as follows: Title: VEGF Gene Therapy Improves Exercise Time, Ischemia, and Symptoms in Patients with Refractory Angina: Results of the Phase II EXACT Trial Lead Presenter: Kenta Nakamura, M.D., Associate Professor at the University of Washington Date and Time: Thursday, May 2, 2024; 9:31-9:38 AM PT Location: Long Beach Convention Center, 104A, First Level An additional press release from SCAI on the Phase 2 EXACT Trial results and poster session is available at . The Circulation: Cardiovascular Interventions full article titled “Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial” is available at . About XC001 XC001 is designed to promote new blood vessels in the heart that will bypass diseased blood vessels and improve blood flow. By restoring blood flow, chest pain associated with refractory angina may decrease, potentially improving patients’ quality of life by enabling them to engage in daily physical activities that would otherwise cause pain. XC001 is designed to avoid toxicity issues observed with other gene therapies through a strategy of one‑time, local administration. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects. About the EXACT Study The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial was a Phase 1/2 multicenter, open‑label, single‑arm trial. Twelve subjects (n=3 per dose cohort) who have refractory angina were enrolled into four ascending dose groups, followed by an expansion phase of the trial in which additional subjects were enrolled at the highest tolerated dose (1 x 1011 vp, the highest tested dose). In the EXACT trial, this investigational gene therapy was administered directly to the heart muscle through a mini‑thoracotomy by a cardiac surgeon. About Chronic Refractory Angina In the United States, coronary artery disease is a leading cause of death and disability. Chronic angina pectoris occurs when the heart muscle does not receive sufficient oxygen resulting in chest pain. This is usually due to atherosclerotic plaques that block the coronary arteries. Refractory angina is a growing problem that occurs in patients with chronic angina who are symptomatic despite optimal medical therapy and are no longer eligible for mechanical interventions like percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). These patients currently have no treatment options and are frequently highly symptomatic, which severely impacts their quality of life, and may exacerbate comorbidities and cause further deterioration of their health status. Refractory angina results in significant consumption of healthcare resources, including visits to the emergency department as a result of patients’ chest pain. About XyloCor XyloCor Therapeutics, Inc. is a private, clinical‑stage biopharmaceutical company developing potential best‑in‑class gene therapies to transform outcomes for patients with cardiovascular disease. The Company’s lead product candidate, XC001, is in clinical development to investigate use for patients with refractory angina for whom there are no treatment options. XyloCor has a second preclinical investigational product, XC002, in discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co‑founded by Ronald Crystal, M.D., and Todd Rosengart, M.D., has an exclusive license from Cornell University. For more information, visit .

临床结果基因疗法临床2期引进/卖出

2023-08-25

·BioSpace

XyloCor Therapeutics Presents Phase 2 Data Highlighting Safety and Efficacy of XC001 at the European Society of Cardiology (ESC) Congress 2023

Positive Phase 2 EXACT Trial results at 6-months underscore significant potential of investigational therapy in refractory angina Six-month data have since been sustained out to 12-months supporting durability of XC001 safety and efficacy pro > XC001 targets unmet medical need among patients with refractory angina who have a debilitating quality-of-life burden and no available treatment options WAYNE, PA.--(BUSINESS WIRE)-- XyloCor Therapeutics, Inc., a clinical‑stage biopharmaceutical company developing novel gene therapies for cardiovascular disease, today presented results from the Phase 2 portion of its Phase 1/2 clinical trial (EXACT) of its lead gene therapy candidate XC001 (encoberminogene rezmadenovec) for refractory angina at the European Society of Cardiology (ESC) Congress 2023. During the ESC Congress poster session, Dr. Thomas Povsic, Principal Investigator of the EXACT trial, presented the primary six-month outcome data from the recently completed EXACT trial, which demonstrated that treatment with XC001 resulted in improvements across all key efficacy endpoints. The findings underscore its strong potential as a novel therapeutic approach for the treatment of this disabling condition. XC001 is a one‑time gene therapy designed to reduce ischemic burden by creating new blood vessels in the heart through the local expression of multiple vascular endothelial growth factor (VEGF) isoforms. In the Phase 2 portion of the EXACT trial, 32 patients with class II-IV angina were dosed with the maximal dose of XC001 through transepicardial delivery (direct administration to the heart). XC001 met all of its safety and exploratory objectives and showed potential transformative benefits for the patient population. Among the notable topline results presented at the ESC Congress 2023 included: VEGF gene therapy with XC001 administered via minimally invasive transepicardial delivery was generally well tolerated. There were no serious adverse events related to the drug or unexpected serious adverse events related to XC001 administration. Patients demonstrated improvements in key efficacy measures most notably total exercise time, time to the development of ST-depression (an objective measure of ischemia), angina frequency, and reduction in ischemic burden as measured by Positron Emission Tomography (PET) imaging. The six-month results showed that XC001 achieved a clinically meaningful biologic effect, warranting further study in larger randomized clinical trials. “Refractory angina is a debilitating and chronic condition that is growing in prevalence and these patients have exhausted all treatment options,” said Thomas Povsic, M.D., Ph.D., Professor of Medicine, Duke University School of Medicine and National Principal Investigator for the EXACT study. “The six-month results from the EXACT trial – which have now been sustained out to 12 months – demonstrate that gene therapy with XC001 has the potential to be safely administered while improving quality of life for these cardiac patients.” “The clinical research results presented at ESC Congress 2023 highlight XyloCor's continuing efforts to transform the treatment paradigm in refractory angina through the promise of one-time gene therapy,” said Al Gianchetti, President and CEO of XyloCor. “We are excited to share data that provides evidence for angiogenesis and a promising efficacy and tolerability pro XC001. These results strongly support our continued development of this novel therapeutic approach.” Further background and results presented in the ESC Congress 2023 poster session titled “Angiogenic gene therapy for refractory angina: Results of the Epicardial delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) Phase 2 Trial can be found here. About XC001 XC001 is designed to promote new blood vessels in the heart that will bypass diseased blood vessels and improve blood flow. By restoring blood flow, chest pain associated with refractory angina may decrease, potentially improving patients’ quality of life by enabling them to engage in daily physical activities that would otherwise cause pain. XC001 is designed to avoid toxicity issues observed with other gene therapies through a strategy of one‑time, local administration. This approach allows XC001 to achieve higher gene expression in the heart while minimizing systemic vector circulation and associated side effects. About the EXACT Study The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial was a Phase 1/2 multicenter, open‑label, single‑arm trial. Twelve subjects (n=3 per dose cohort) who have refractory angina were enrolled into four ascending dose groups, followed by an expansion phase of the trial in which additional subjects were enrolled at the highest tolerated dose (1 x 1011 vp, the highest tested dose). In the EXACT trial, this investigational gene therapy is administered directly to the heart muscle through a mini‑thoracotomy by a cardiac surgeon. About Chronic Refractory Angina In the United States, coronary artery disease is a leading cause of death and disability. Chronic angina pectoris occurs when the heart muscle does not receive sufficient oxygen resulting in chest pain. This is usually due to atherosclerotic plaques that block the coronary arteries. Refractory angina is a growing problem that occurs in patients with chronic angina who are symptomatic despite optimal medical therapy and are no longer eligible for mechanical interventions like percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). These patients currently have no treatment options and are frequently highly symptomatic, which severely impacts their quality of life, and may exacerbate comorbidities and cause further deterioration of their health status. Refractory angina results in significant consumption of healthcare resources, including visits to the emergency department as a result of patients’ chest pain. About XyloCor XyloCor Therapeutics, Inc. is a private, clinical‑stage biopharmaceutical company developing potential best‑in‑class gene therapies to transform outcomes for patients with cardiovascular disease. The Company’s lead product candidate, XC001, is in clinical development to investigate use for patients with refractory angina for whom there are no treatment options. XyloCor has a second preclinical investigational product, XC002, in discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co‑founded by Ronald Crystal, M.D., and Todd Rosengart, M.D., has an exclusive license from Cornell University. For more information, visit . View source version on businesswire.com: Contacts Corporate and Investor Relations: A. Brian Davis, XyloCor Therapeutics, Inc. brian.davis@xylocor.com 610-541-2056 Media: Mike Beyer Sam Brown Inc. Healthcare Communications mikebeyer@sambrown.com 312-961-2502 Source: XyloCor Therapeutics, Inc. View this news release online at:

临床结果基因疗法引进/卖出临床2期

2023-08-07

·药明康德

可让患者停药一年多的基因疗法；治疗顽固性心绞痛的一次性基因疗法... | 一周盘点

▎药明康德内容团队编辑本期看点1. 用于治疗湿性年龄相关性黄斑变性（AMD）的在研基因疗法4D-150的早期临床结果积极，在最高测试剂量下，100%的可评估患者在36周时无需补充注射抗血管内皮生长因子（VEGF）疗法。2. 用于治疗顽固性心绞痛的一次性基因疗法1期临床试验结果积极，最高剂量将进入2期临床研究。药明康德内容团队整理4D-150：公布1/2期临床试验的新中期数据 4D Molecular Therapeutics公司公布了其玻璃体内注射的双重基因疗法4D-150用于治疗湿性AMD的1/2期临床试验的新中期数据。湿性AMD是一种影响视网膜中央黄斑部的病症，主要由脉络膜新生血管所导致，即在黄斑部有不正常的血管增生。4D-150由表达阿柏西普和抗VEGF-C的RNAi有效载荷以及能够在玻璃体内进行递送的专有载体R100组成，能够抑制4种血管生成因子：VEGFA、B、C和PlGF。新闻稿指出，4D-150是首款旨在抑制驱动血管生成的所有四种VEGF相关分子的视网膜基因疗法。此次公布的数据显示，36周时，在抗VEGF需求较高的患者群体中，最高测试剂量3E10 vg/眼组可评估患者中100%（4/4）的患者无需补充注射抗VEGF疗法，平均视网膜中央次视野厚度（CST）有临床意义的减少。该组患者36周后的疗效评估显示，4名可评估患者中有3名在一年后仍无需补充注射抗VEGF疗法，1名患者在最长80周的随访期间仍不需要补充注射。较低剂量（1E10、6E9 vg/眼）的4D-150也非常有效，10名患者中有5名无需补充注射抗VEGF疗法，36周内平均每年补充注射抗VEGF疗法的比例降低了71%。所有剂量玻璃体内注射的4D-150的耐受性都很好，在36周的随访期间没有出现≥1级炎症细胞、低血压、剂量限制性毒性或与治疗相关的严重不良事件（SAE）。▲4D-150的临床疗效终点（图片来源：参考资料[1]）XC001：公布1期临床试验数据XyloCor Therapeutics公司公布了其在研、一次性基因疗法XC001治疗顽固性心绞痛患者的1期临床试验结果。慢性心绞痛是由于心脏肌肉无法获得足够氧气而导致胸痛的产生。顽固性心绞痛指的是那些即便经过药物治疗仍存有症状，且已无法进行像是冠状动脉介入治疗与冠状动脉搭桥手术物理性疗法的患者。这些患者目前没有治疗选项，患者发病率高，经常出现包括胸痛、呼吸短促以及易疲劳等症状，严重影响其生活品质。XC001旨在在心脏中特异性表达能够促进血管增生的VEGF，从而促进心脏的血管生成。通过增强血管增生，XC001有望提高心脏的血液与氧气供应，从而缓解顽固性心绞痛症状。此次公布的结果显示，通过小型胸腔切开术从心外膜给药XC001是可行的。2020年6月2日至2021年6月25日，12名患者被纳入4个给药组，7名患者发生了17起严重不良事件，但均与研究药物无关。4名患者中的6例严重不良事件与开胸手术有关，3例非严重不良事件可能与研究药物有关。接受2种较高剂量药物的患者在总运动时间、心肌灌注缺损或心绞痛频率方面都有改善，该研究中的最高剂量将进入2期临床试验。LX2020：IND申请获得FDA许可LX2020是LESEO Therapeutics公司开发的基于AAVrh10候选基因疗法。该疗法旨在通过静脉注射将功能性PKP2基因输送到心肌，以治疗由PKP2基因变异引起的心律失常性心肌病（PKP2-ACM）。PKP2-ACM是一种遗传性心脏病，主要特征是心肌细胞缺失，心肌被纤维组织和脂肪沉积取代。ACM可由多个桥粒（desmosome）相关基因的变异引起，其中PKP2基因的变异占大多数。这些基因变异会损害心脏中参与细胞间粘附的膜蛋白复合物的结构和功能以及心室心肌的结构完整性，从而导致心肌细胞的死亡和纤维化、心脏功能障碍、心律失常和猝死。目前，还没有获批疗法来减缓、预防或逆转PKP2-ACM患者的疾病进展。在临床前研究中，LX2020改善了心脏组织的组成和完整性，缓解了心律失常，改善了左右心室功能，提高了PKP2-ACM模型小鼠的存活率。近日，该疗法的IND申请获得FDA许可，即将展开为期52周的开放标签、剂量递增、多中心1/2期临床试验，以确定LX2020在患有PKP2-ACM的成年患者中的安全性和耐受性。ALTB-268：公布1期临床试验数据AltruBio公司公布了其免疫检查点增强剂（ICE）ALTB-268治疗溃疡性结肠炎的1期临床试验的积极顶线数据。ALTB-268是一种四价PSGL-1激动抗体，可通过抑制T细胞效应功能、促进T细胞衰竭和凋亡来优先下调慢性激活的T细胞。ALTB-268能在不进行系统抑制的情况下，从源头治疗免疫疾病，帮助免疫系统恢复平衡状态。LTB-268采用皮下注射配方，便于患者使用。此次公布的结果显示，ALTB-268在健康受试者中的耐受性良好，未发生严重不良事件。此外，ALTB-268的生物活性高于该公司开发的首个ICE分子ALTB-168，支持皮下注射的给药方式。QN-302：IND申请获得FDA许可QN-302是Qualigen Therapeutics公司开发的潜在“best-in-class”的小分子脱氧鸟嘌呤四联体（G4，G-quadruplex）选择性转录抑制剂，用于治疗表达G4的实体肿瘤，如胰腺导管腺癌、前列腺癌、肉瘤等。QN-302能够稳定多种肿瘤类型中癌基因启动子区域中普遍存在的G4复合物，阻碍含G4的癌症基因的转录，并有望提供一种不限癌种的临床治疗方法。今年1月，美国FDA授予QN-302孤儿药资格，用于治疗胰腺癌。近日，QN-302的IND申请已获得美国FDA的许可。基于这一批准，公司计划在2023年下半年针对晚期或转移性实体瘤患者启动1期临床试验。INI-2004：IND申请获得FDA许可INI-2004是Inimmune公司开发的TLR4激动剂候选产品，用于治疗过敏性鼻炎。INI-2004是一种不针对特定过敏原的免疫疗法，能结合并激活TLR4。经鼻内给药后，INI-2004可显著降低临床前动物模型的过敏性鼻炎指标，包括气道阻力、嗜酸性粒细胞流入以及与过敏性鼻炎发病机制有关的细胞因子的产生。近日，INI-2004的IND申请已获得美国FDA的许可，即将启动1b期临床试验。大家都在看作为药明康德旗下专注于细胞和基因疗法的CTDMO，药明生基致力于加速和变革基因和细胞治疗及其他高端治疗的开发、测试、生产和商业化。药明生基能够助力全球客户将更多创新疗法早日推向市场，造福病患。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲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] 4DMT Presents Additional Positive Interim Data from Intravitreal 4D-150 Phase 1/2 PRISM Clinical Trial in Patients with Wet AMD at ASRS 2023. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/07/29/2714505/0/en/4DMT-Presents-Additional-Positive-Interim-Data-from-Intravitreal-4D-150-Phase-1-2-PRISM-Clinical-Trial-in-Patients-with-Wet-AMD-at-ASRS-2023.html[2] IO Biotech Announces First Patient Dosed in Investigator-Initiated Phase 1 Trial at University of California Davis Comprehensive Cancer Center. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/07/28/2713108/0/en/IO-Biotech-Announces-First-Patient-Dosed-in-Investigator-Initiated-Phase-1-Trial-at-University-of-California-Davis-Comprehensive-Cancer-Center.html[3] Ultragenyx Announces Initiation of Dosing in Second Cohort of Pivotal Phase 1/2/3 Cyprus2+ Trial Evaluating UX701 Gene Therapy for the Treatment of Wilson Disease. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/07/31/2714842/20739/en/Ultragenyx-Announces-Initiation-of-Dosing-in-Second-Cohort-of-Pivotal-Phase-1-2-3-Cyprus2-Trial-Evaluating-UX701-Gene-Therapy-for-the-Treatment-of-Wilson-Disease.html[4] AltruBio Announces Positive Topline Data from Phase 1 Trial of Immune Checkpoint Enhancer ALTB-268 for the Treatment of Ulcerative Colitis. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/08/01/2715771/0/en/AltruBio-Announces-Positive-Topline-Data-from-Phase-1-Trial-of-Immune-Checkpoint-Enhancer-ALTB-268-for-the-Treatment-of-Ulcerative-Colitis.html[5] Pipeline Therapeutics Announces First Subject Dosed with PIPE-791 in Phase 1 Study. Retrieved August 6，2023，from https://www.businesswire.com/news/home/20230801836333/en[6] Entrada Therapeutics Receives Authorization in the United Kingdom to Initiate Phase 1 Clinical Trial of ENTR-601-44 for the Potential Treatment of Duchenne Muscular Dystrophy. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/08/01/2715645/0/en/Entrada-Therapeutics-Receives-Authorization-in-the-United-Kingdom-to-Initiate-Phase-1-Clinical-Trial-of-ENTR-601-44-for-the-Potential-Treatment-of-Duchenne-Muscular-Dystrophy.html[7] IDEAYA and Amgen Achieve First-Patient-In for Clinical Evaluation of IDE397 (MAT2A) and AMG 193 (PRMT5(MTA)) Combination in MTAP(-/-) Tumors. Retrieved August 6，2023，from https://www.prnewswire.com/news-releases/ideaya-and-amgen-achieve-first-patient-in-for-clinical-evaluation-of-ide397-mat2a-and-amg-193-prmt5mta-combination-in-mtap---tumors-301891206.html[8] AskBio Announces First Patient Dosed in Phase 1 / Phase 2 Trial of AB-1003 Gene Therapy for Limb-Girdle Muscular Dystrophy Type 2I/R9 (LGMD2I/R9). Retrieved August 6，2023，from https://www.prnewswire.com/news-releases/askbio-announces-first-patient-dosed-in-phase-1--phase-2-trial-of-ab-1003-gene-therapy-for-limb-girdle-muscular-dystrophy-type-2ir9-lgmd2ir9-301892324.html[9] Celsius Therapeutics Announces Initiation of Dosing in Phase 1 Clinical Trial of CEL383, an Anti-TREM1 Antibody for the Treatment of Inflammatory Bowel Disease. Retrieved August 6，2023，from https://www.businesswire.com/news/home/20230803586891/en[10] LEXEO Therapeutics Announces FDA Clearance of IND for LX2020, an AAV-based Gene Therapy Candidate for PKP2 Arrhythmogenic Cardiomyopathy. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/08/01/2715695/0/en/LEXEO-Therapeutics-Announces-FDA-Clearance-of-IND-for-LX2020-an-AAV-based-Gene-Therapy-Candidate-for-PKP2-Arrhythmogenic-Cardiomyopathy.html[11] Qualigen Therapeutics Announces US FDA IND Clearance to Initiate Phase 1 Clinical Trial of QN-302 for Treatment of Advanced or Metastatic Solid Tumors. Retrieved August 6，2023，from https://www.globenewswire.com/news-release/2023/08/01/2715847/0/en/Qualigen-Therapeutics-Announces-US-FDA-IND-Clearance-to-Initiate-Phase-1-Clinical-Trial-of-QN-302-for-Treatment-of-Advanced-or-Metastatic-Solid-Tumors.html[12] Inimmune Corporation announces First Subject Dosed in First-in-Human Phase 1 Clinical Trial of its novel intranasal TLR4 agonist, INI-2004, for the Treatment of Allergic Rhinitis and FDA Clearance of IND application for INI-2004. Retrieved August 6，2023，from https://www.prnewswire.com/news-releases/inimmune-corporation-announces-first-subject-dosed-in-first-in-human-phase-1-clinical-trial-of-its-novel-intranasal-tlr4-agonist-ini-2004-for-the-treatment-of-allergic-rhinitis-and-fda-clearance-of-ind-application-for-ini-2004-301891598.html[13] Results from XyloCor Therapeutics’ Phase 1 Portion of EXACT Trial of XC001 for Cardiovascular Disease Published in Circulation: Cardiovascular Interventions. Retrieved August 6，2023，from https://www.businesswire.com/news/home/20230803967906/en[14] Povsic TJ, Henry TD, Traverse JH, et al. EXACT Trial: Results of the Phase 1 Dose-Escalation Study [published online ahead of print, 2023 Jul 28]. Circ Cardiovasc Interv. 2023;e012997. doi:10.1161/CIRCINTERVENTIONS.123.012997疫苗的免责声明：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

基因疗法临床结果临床1期临床2期

100 项与 Encoberminogene Rezmadenovec 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
心绞痛	临床2期	美国	-	2021-07-21
冠心病	临床2期	美国	Xylocor Therapeutics, Inc.	2020-01-24
缺血	临床2期	美国	Xylocor Therapeutics, Inc.	2020-01-24
难治性心绞痛	临床2期	美国	Xylocor Therapeutics, Inc.	2020-01-24

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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


EXACT (ESC2023)	临床2期	难治性心绞痛	-	XC001 gene therapy	積壓範壓餘醖廠齋簾簾(窪觸艱製襯鬱衊簾壓衊) = 壓顧鏇選製獵範遞艱鑰糧構鏇遞選壓鏇夢憲廠 (網簾壓選獵壓壓鑰齋顧, 31.3 ~ 139.7)	积极	2023-08-25
phase 1/2 clinical trial (ASGCT2021)	临床3期	难治性心绞痛 VEGF	-	XC001	網艱壓衊糧鏇鏇淵鑰糧(廠窪壓製繭築壓襯艱選) = vector-derived VEGF secreted by the cardiomyocytes was capable of stimulating a VEGF-responsive cell line similarly to control recombinant VEGF protein 鹽範淵窪獵築選鹹鬱鏇 (簾鹽衊窪糧築壓窪襯製 ) 更多	-	2021-04-27
phase 1/2 clinical trial (ASGCT2021)	临床3期	难治性心绞痛 VEGF	-	XC001		-	2021-04-27