Evommune, Inc.

今日，Jasper Therapeutics公布其进行中SPOTLIGHT临床1b/2a期研究的初步数据。分析显示，慢性诱发性荨麻疹（CIndU）患者在接受其在研药物briquilimab皮下注射后1周便观察到完全缓解（CR），且93%的患者在接受治疗后6周达成缓解。该公司已获得监管批准在SPOTLIGHT研究中招募患者接受更高剂量药物的治疗。Jasper Therapeutics预计将在2025年上半年公布SPOTLIGHT研究的全部数据。 荨麻疹，又称风疹块，是一种引起皮肤瘙痒和肿块的反应。慢性荨麻疹的特征是斑块持续时间超过六周，并常在数月甚至数年间反复出现。最初，这些斑块通常表现为瘙痒的小块，逐渐发展为大小不一的肿胀斑块，且会不定期出现和消失，给患者带来显著的不适，影响其睡眠及日常生活。许多患者会使用抗组胺药等药物来缓解瘙痒。慢性荨麻疹分为慢性自发性荨麻疹（CSU）和CIndU，后者是由特定诱因（如冷、热、运动、压力、阳光、振动、水等）引发的荨麻疹，以风团和/或血管性水肿为主要表现。根据诱因不同，CIndU可分为物理性和非物理性两大类。物理性荨麻疹包括最常见的症状性皮肤划痕症（SD）和冷接触性荨麻疹（ColdU）等亚型。前者因机械性剪切力作用而在数分钟内形成条状风团，后者则在皮肤接触冷物质（如风、液体或空气）后于接触部位出现局部瘙痒的风团或血管性水肿。 SPOTLIGHT研究是一项1b/2a期开放标签临床试验，旨在评估单剂量皮下注射briquilimab对患有冷性荨麻疹或症状性皮肤划痕症成年患者的疗效与安全性，这些患者对抗组胺药耐药。该研究预计招募27例患者，分为三个剂量组，包含40毫克、120毫克和180毫克组。主要终点是briquilimab的安全性和耐受性，次要终点包含药物的临床活性和药代动力学/药效学（PK/PD）特征，包括测量患者血清中的类胰蛋白酶（tryptase）水平，类胰蛋白酶是主要由肥大细胞分泌的一种炎症介质。为了评估临床活性，受试者的症状是通过在给药前以及给药后12周内的特定时间点，对患者进行激发检测（provocation testing）进行。 截至2024年10月10日，已有15名受试者入组并接受单剂量briquilimab皮下注射（40毫克，n=3；120毫克，n=12），所有受试者在给药后均接受了至少6周的随访。在12名接受120毫克剂量治疗的受试者中，4名为ColdU亚型，8名为SD亚型。根据激发阈值测试评估，这些入组受试者的疾病负担较高。 分析显示，研究中两个剂量组的15名受试者中有14名（93%）在治疗后6周的初步分析期内对激发检测产生了临床应答。120毫克剂量组中的12名患者中有10名（83%）达到了完全缓解（CR）。120毫克组患者中有1名达成部分缓解（PR）。另一方面，40毫克组中有1名患者达成CR，2名患者达成PR。 值得一提的是，患者在给药后1周便在测试中观察到完全缓解。早在第1周评估时就观察到120毫克剂量组患者的类胰蛋白酶水平显著降低，并与患者临床应答的开始相关。与基线相较，在治疗后2周观察到该组患者的平均类胰蛋白酶水平降低幅度最高达66%。在第6周评估时，观察到患者的平均类胰蛋白酶水平降低31%，12名受试者中有7名（58%）继续保持临床缓解（CR=6，PR=1）。 研究中，briquilimab展现良好的耐受性。未报告任何严重不良事件或3级不良事件。此外，未报告与头发或皮肤颜色变化、过敏或贫血相关的不良事件。观察到中性粒细胞计数轻微下降，但没有受试者的中性粒细胞计数低于1500。 柏林大学医学院教授Martin Metz博士表示：“初步临床数据显示，使用briquilimab治疗后可在短时间内带来显著的临床益处，尤其对于那些抗组胺药无效的CIndU患者群体而言，这一结果极具吸引力。” Briquilimab是一种非糖基化单克隆抗体，可通过靶向细胞表面受体c-Kit（也称为CD117）以避免与干细胞因子结合，从而阻断肥大细胞中的关键生存信号，造成细胞凋亡与耗竭，从而消除肥大细胞驱动疾病（如慢性荨麻疹）中炎症反应的潜在来源。Jasper目前正在临床试验中检视briquilimab用以治疗CSU或CIndU患者，并正在启动一项针对哮喘患者的临床试验。迄今为止，briquilimab已在超过160名患者和健康志愿者中展示出其安全性与有效性，展现了作为CIndU潜在治疗方案的前景。此外，briquilimab还具有作为重度联合免疫缺陷（SCID）、急性髓系白血病（AML）、骨髓增生异常综合征（MDS）、范可尼贫血（FA）和镰刀型细胞贫血病（SCD）预处理剂的潜力。 除了Jasper Therapeutics，目前正在开发疗法用以治疗CIndU的还有Celldex Therapeutics。该公司在今年7月宣布其在研Kit靶向单抗barzolvolimab在2期临床试验中用以治疗ColdU和SD患者时达成主要疗效终点。即在第12周时，与安慰剂相比，接受barzolvolimab治疗的患者中，诱发因素检测未导致荨麻疹的患者百分比具有统计学显著差异。今年4月，Incyte和Escient Pharmaceuticals达成协议，Incyte囊获后者的潜在“first-in-class”小分子MRGPRX2拮抗剂EP262。MRGPRX2是肥大细胞上表达的一种受体，可由包括感觉神经元和其他细胞类型释放的多种配体激活。通过阻断MRGPRX2和肥大细胞颗粒释放，EP262具潜力治疗多种肥大细胞介导的疾病。目前，EP262用于治疗CIndU的1b/2期临床试验正在进行中。而Evommune公司也在今年2月启动其MRGPRX2小分子拮抗剂EVO756用以治疗CIndU患者的临床2期试验。 参考资料： [1] Jasper Therapeutics Reports Positive Data from SPOTLIGHT Study of Briquilimab in Chronic Inducible Urticaria. Retrieved October 14, 2024 from https://www.globenewswire.com/news-release/2024/10/14/2962446/0/en/Jasper-Therapeutics-Reports-Positive-Data-from-SPOTLIGHT-Study-of-Briquilimab-in-Chronic-Inducible-Urticaria.html [2] Jasper Therapeutics: Preliminary SPOTLIGHT Results. Retrieved October 14, 2024 from https://ir.jaspertx.com/static-files/f162fd13-7a06-47d7-bbbf-331ed924de0b [3] 关于慢性诱导性荨麻疹有哪些分类分型，又有怎样的临床表现？Retrieved October 14, 2024 from http://www.bra-cdche.com/html/show-838.html [4] 慢性荨麻疹. Retrieved October 14, 2024 from https://www.mayoclinic.org/zh-hans/diseases-conditions/chronic-hives/symptoms-causes/syc-20352719 [5] Evommune Initiates Phase 2 Trial of EVO756, an Oral MRGPRX2 Antagonist, in Chronic Inducible Urticaria. Retrieved October 14, 2024 from https://www.evommune.com/wp-content/uploads/2024/09/21_Evommune_EVO756_CindU_Phase_2_Trial.pdf 内容来源于网络，如有侵权，请联系删除。

PALO ALTO, CA, USA I September 3, 2024 I Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced the enrollment of the first patient in a Phase 2 trial of EVO756 in adults with CIndU. EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2) and represents a new, targeted approach with the potential for once-daily oral administration without the serious side effects observed with other therapies. “As we continue to execute on our clinical development plans for EVO756, we are commencing this Phase 2 trial in 15 study sites across the United States. CIndU patients have limited treatment options, and we believe a novel, highly potent, selective agent, that can be orally administered once daily, could provide patients with major therapeutic benefit,” said J. Mark Jackson, MD, Vice President, Clinical Development at Evommune. The multi-center trial is designed to evaluate the safety and efficacy of EVO756 in approximately 30 patients with either symptomatic dermographism or cold urticaria, the two most common forms of CIndU. Efficacy endpoints include changes from baseline in disease specific provocation thresholds that are used as objective markers to quantify disease severity and response to treatment. EVO756 will be administered orally, once daily, for four weeks, and will be evaluated for safety and efficacy at weekly visits during treatment, with patients serving as their own control. “Initiation of this trial marks another important milestone in dedication to delivering the therapeutic potential of MRGPRX2 antagonism to patients in a broad range of mast cell-mediated disorders,” said Daniel J. Burge, M.D., Senior Vice President, Clinical Development at Evommune. “Following the success of our proof-of-concept study with EVO756 earlier this year, we are also on track to initiate a Phase 2b trial in chronic spontaneous urticaria in the second quarter of 2025.” About Chronic Urticaria Chronic urticaria, defined as urticaria persisting for more than 6 weeks, is a substantial burden for patients, their families and careers, the healthcare system, and society. Chronic urticaria manifests with very itchy hives that may vary in size and can result in sleep deprivation, anxiety, depression, lack of energy, and social isolation which can result in a significant deterioration in the quality of life. Some patients with chronic urticaria may also develop swelling deeper under the skin or in other tissues (angioedema). There are two main forms of chronic urticaria. In chronic spontaneous urticaria (CSU), hives occur spontaneously, without known triggers. In chronic inducible urticaria (CIndU), hives are induced by specific triggers such as cold exposure (cold urticaria) or touch (symptomatic dermographism), among others. Chronic urticaria is a mast cell-driven disease. Activated mast cells release histamine along with other mediators, such as platelet-activating factor and cytokines, resulting in sensory nerve activation, vasodilation, plasma extravasation, and recruitment of cells to the urticarial lesion. About EVO756 EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). MRGPRX2 is most abundantly found on mast cells and peripheral sensory neurons. MRGPRX2 can trigger IgE-independent activation (degranulation) via multiple ligands, which can lead to a variety of symptoms depending on the tissue that is affected. Evommune’s pre-clinical data demonstrates that by blocking activation of MRGPRX2 via all disease relevant ligand categories, EVO756 can prevent the degranulation of mast cells. EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell mediated diseases. In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis. About Evommune, Inc. Evommune, Inc., a Palo Alto based biotech company, is creating game-changing science to treat immune-mediated inflammatory diseases by discovering, developing, and delivering therapies that address symptoms and halt progressive disease. For more information, please visit www.evommune.com . SOURCE: Evommune

PALO ALTO, Calf., July 16, 2024. Evommune, Inc., a clinical stage biotechnology company discovering and developing new ways to treat immune-mediated inflammatory diseases, today announced positive results of its first-in-human proof-of-concept study with EVO756. By blocking MRGPRX2 activation and degranulation of mast cells, EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell-mediated diseases. Evommune is planning to present a comprehensive data set of this trial at a peer-review scientific meeting in the fall of 2024. "The data from our proof-of-concept trial exceeded our expectations, and we now plan to initiate multiple clinical trials of EVO756, including a Phase 2b study in chronic spontaneous urticaria (CSU) patients during the first half of 2025," said Eugene Bauer, M.D., Chief Medical Officer at Evommune. "We believe we have a novel, highly potent and selective agent that can be orally administered once daily, with broad opportunity for patients suffering from various mast-cell mediated diseases." The proof-of-concept study is a randomized, double-blind, placebo-controlled single and multiple ascending dose (SAD and MAD) study in normal healthy adults and assessed the safety, tolerability, pharmacokinetics and pharmacodynamics/target engagement of orally administered EVO756. Doses from 1 mg to 500 mg were administered in ascending order across 7 cohorts of 8 subjects each (6 active, 2 placebo). In the MAD cohorts completed to date, ascending doses of 10 mg, 30 mg, 100 mg and 240 mg BID have been administered across 4 cohorts of 16 subjects each (12 active and 4 placebo). The pharmacodynamic potential of EVO756 on mast cell degranulation was assessed in a skin challenge test, in which icatibant, a known ligand of the MRGPRX2 receptor, was administered intradermally, resulting in measurable skin responses in all MAD participants. Multiple experimental methods have determined that mast cell degranulation caused by icatibant is representative to changes associated with MRGPRX2 disease-relevant endogenous ligands. This portion of the study allowed for an evaluation of target engagement and activity in a highly controlled setting and had the benefit of mimicking the potential impact of EVO756 versus placebo in inducible urticarias. "EVO756's excellent safety profile and potential for a once daily oral dosing provide continued excitement around this new class of therapies in inflammatory diseases. As expected, these data further support the hypothesis that blockade of the MRGPRX2 receptor and its subsequent downstream effect has the potential to treat the root cause of inflammation, offering greater relief than currently available treatments," commented Sarbjit Saini, M.D., Professor of Medicine at Johns Hopkins University in Baltimore, Maryland. About EVO756 EVO756 is a potent, highly selective small molecule antagonist of mas-related G-protein coupled receptor X2 (MRGPRX2). MRGPRX2 is most abundantly found on mast cells and peripheral sensory neurons. MRGPRX2 can trigger IgE-independent activation (degranulation) via multiple ligands, which can lead to a variety of symptoms depending on the tissue that is affected. Evommune's pre-clinical data demonstrates that by blocking activation of MRGPRX2 and degranulation of mast cells, EVO756 has the potential to be a first-in-class oral treatment for a variety of mast cell mediated diseases. In addition, due to its unique function on peripheral sensory neurons, EVO756 could provide fast relief of itch associated with inflammatory diseases, such as atopic dermatitis. About Evommune, Inc. Evommune, Inc., a Palo Alto based biotech company, is creating game-changing science to treat immune-mediated inflammatory diseases by discovering, developing, and delivering therapies that address symptoms and halt progressive disease. For more information, please visit Evommune.com. SOURCE Evommune, Inc Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.