生物制药公司ORYZON宣布在《柳叶刀血液学》杂志上发表Iadademstat的IIa期ALICE最终结果-动脉网

ORYZON Announces Journal Publication of Final Phase IIa ALICE Results with Iadademstat in The Lancet Hematology

BioSpace 等信源发布 2024-06-03 16:51

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The Phase IIa study ALICE evaluated the combination of iadademstat plus azacitidine in newly diagnosed, unfit patients with acute myeloid leukemia (AML)

IIa期研究ALICE评估了iadademstat联合阿扎胞苷治疗新诊断的不健康急性髓细胞白血病（AML）患者的疗效

The combination showed substantial antileukemic activity with deep responses and a manageable safety profile, including in patients with high-risk prognostic factors

该组合显示出显着的抗白血病活性，具有深度反应和可控的安全性，包括具有高危预后因素的患者

Iadademstat continues to be studied in 1L unfit AML patients through an investigator-initiated study with Oregon Health & Science University (OHSU)

通过俄勒冈州健康与科学大学（OHSU）的一项由研究者发起的研究，Iadademstat继续对1L不适合的AML患者进行研究

MADRID and CAMBRIDGE, Mass., June 03, 2024 (GLOBE NEWSWIRE) -- ORYZON Genomics S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, announced today that the final results of the Phase IIa ALICE study evaluating iadademstat in combination with azacitidine in unfit patients with newly diagnosed acute myeloid leukemia (AML) were published online in The Lancet Hematology.

马德里和剑桥，马萨诸塞州，2024年6月3日（环球通讯社）--ORYZON Genomics S.A.（ISIN代码：ES0167733015，ORY），一家临床阶段的生物制药公司，利用表观遗传学开发治疗严重未满足医疗需求的疾病，今天宣布，IIa期ALICE研究的最终结果评估了iadademstat联合阿扎胞苷治疗不适合的新诊断急性髓细胞白血病（AML）患者，并在《柳叶刀血液学》上在线发布。

A summary of the final data from this study had been previously released in an oral presentation at the 2022 American Society for Hematology (ASH) annual meeting, where it was selected as one of the 25 most relevant communications in AML..

这项研究的最终数据摘要先前已在2022年美国血液学会（ASH）年会的口头报告中发布，该报告被选为AML中25个最相关的沟通之一。。

This notable publication is a continuation of Oryzon’s previous pioneering research featured in the Journal of Clinical Oncology (First-in-Human study in AML with iadademstat) and Cancer Cell (Characterization of iadademstat as a potent and selective LSD1 inhibitor), cementing the company’s position at the forefront of epigenetics in oncology and LSD1 innovation..

这篇著名的出版物是Oryzon之前在《临床肿瘤学杂志》（首次使用iadademstat进行AML人体研究）和《癌细胞》（将iadademstat表征为有效且选择性的LSD1抑制剂）上发表的开创性研究的延续，巩固了该公司在肿瘤学表观遗传学和LSD1创新领域的前沿地位。。

Dr. Carlos Buesa, Oryzon’s CEO, stated, “We are thrilled to publish these groundbreaking results in one of the most prestigious journals in clinical oncology. Our study demonstrates that targeting LSD1 is a completely novel anti-leukemic mechanism of action in AML, potentially offering a new therapeutic approach, especially for patients with hard-to-treat forms of the disease such as myelomonocytic leukemias, DNMTs mutations, or TP53 mutations.

Oryzon首席执行官Carlos Buesa博士表示：“我们很高兴在临床肿瘤学最负盛名的期刊之一上发表这些开创性的结果。我们的研究表明，靶向LSD1是AML中一种全新的抗白血病作用机制，可能提供一种新的治疗方法，特别是对于骨髓单核细胞白血病，DNMTs突变或TP53突变等难以治疗的疾病患者。

These patients currently respond poorly to available treatments and may benefit from the innovative treatment option of iadademstat. We want to reiterate our gratitude to the patients, their families and the researchers involved in this study.”.

这些患者目前对可用的治疗反应不佳，可能会受益于iadademstat的创新治疗选择。我们要再次感谢参与这项研究的患者，他们的家人和研究人员。”。

Summary of the main results reported in the publication

出版物中报告的主要结果摘要

The combination of iadademstat with azacitidine induced a high proportion of responses, with 22 (82%) of 27 patients in the efficacy analysis set having an objective response. Notably, 52% of patients had either a complete remission (CR) or complete remission with incomplete hematological recovery (CRi) in the ALICE trial.

iadademstat与阿扎胞苷的联合治疗引起了高比例的反应，疗效分析集中27例患者中有22例（82%）有客观反应。值得注意的是，在ALICE试验中，52%的患者完全缓解（CR）或完全缓解，血液学恢复不完全（CRi）。

For comparison, the percentage of patients who experienced a CR/CRi in the intention-to-treat azacitidine populations was 28% in the acute myeloid leukaemia-001 trial, 28% in the VIALE A trial, and 27% in the Monarch trial..

相比之下，在意向治疗阿扎胞苷人群中经历CR/CRi的患者百分比在急性髓性白血病-001试验中为28%，在VIALE a试验中为28%，在Monarch试验中为27%。。

Most of the responses occurred rapidly (87% by the second assessment) and 36% lasted 12 months or longer. At database lock (1 year after the last patient was enrolled), nine patients were alive and as of February, 2024, five patients remain alive, with three continuing treatment (and in complete remission) under compassionate use after four years..

大多数反应发生迅速（第二次评估为87%），36%持续12个月或更长时间。在数据库锁定时（最后一名患者入选后1年），有9名患者还活着，截至2024年2月，有5名患者仍然活着，四年后有3名患者在同情下继续治疗（并完全缓解）。。

The CR/CRi responses in ALICE were generally deep, as determined by the high rate of measurable residual disease (MRD) negativity (91% in the evaluable samples), which is associated with improved survival.

ALICE中的CR/CRi反应通常很深，这是由可测量的残留疾病（MRD）阴性率高（可评估样本中为91%）决定的，这与生存率的提高有关。

Remarkably, responses were seen across the entire adverse prognostic mutational landscape. Of note are the responses in specific subgroups:

值得注意的是，在整个不良预后突变领域都观察到了反应。值得注意的是特定小组的回应：

Three patients with M5 AML (a population primary refractory to venetoclax and azacitidine) had CR/CRi with iadademstat plus azacitidine, with 100% measurable residual disease negativity.

三名M5 AML患者（主要对venetoclax和阿扎胞苷难治的人群）使用iadademstat加阿扎胞苷进行CR/CRi，100%可测量的残留疾病阴性。

In patients with AML with TP53 mutations in combination with a complex karyotype or high variant allele frequency, or both, CR/CRi was reached in 63%, with a duration of response of 7.9 months and a median overall survival of 10 months.

在具有TP53突变并伴有复杂核型或高变异等位基因频率或两者的AML患者中，CR/CRi达到63%，反应持续时间为7.9个月，中位总生存期为10个月。

Responses in leukemias harboring other poorer-prognosis mutations were also encouraging. All seven patients harboring a mutation or mutations in the RAS pathway responded, with a median overall survival of 467 days. Patients harboring mutations in DNM3TA (n=7), NPM1 (n=4), and RUNX (n=3) had 100% response rates, mostly CR or CRi..

携带其他预后较差突变的白血病的反应也令人鼓舞。所有7名在RAS途径中携带突变或突变的患者均有反应，中位总生存期为467天。携带DNM3TA（n=7），NPM1（n=4）和RUNX（n=3）突变的患者有100%的缓解率，主要是CR或CRi。。

A temporary link to access the online publication for free can be found here.

可以在此处找到免费访问在线出版物的临时链接。

As a continuation of ALICE, Oryzon is further expanding the clinical development of iadademstat in 1L unfit AML through an Investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU). This trial is a Phase Ib dose-finding study to evaluate iadademstat in combination with the SoC, venetoclax and azacitidine, in first-line AML patients and is expected to begin enrolling patients in the coming weeks..

作为ALICE的延续，Oryzon正在通过由俄勒冈州健康与科学大学（OHSU）领导的研究者发起的研究（IIS），进一步扩大iadademstat在1L不适合的AML中的临床开发。该试验是一项Ib期剂量发现研究，旨在评估iadademstat联合SoC，venetoclax和阿扎胞苷治疗一线AML患者，预计将在未来几周开始招募患者。。

Iadademstat is currently being evaluated also in combination with gilteritinib in relapsed/refractory AML patients harboring a FLT3 mutation in the FRIDA study, an open-label, multicenter Phase Ib trial being conducted in the US and which plans to accrue up to approximately 45 patients. The first two cohorts have been completed (thirteen patients), and the combination was safe and showed strong antileukemic activity.

在FRIDA研究中，Iadademstat目前也正在与吉特替尼联合评估复发/难治性AML患者的FLT3突变，这是一项在美国进行的开放标签多中心Ib期试验，计划累积约45名患者。前两个队列已经完成（13名患者），并且该组合是安全的并且显示出强烈的抗白血病活性。

Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity, and a third cohort has been started and is recruiting. Preliminary results from this trial will be presented at the upcoming European Hematology Association (EHA) 2024 congress in June..

根据FDA的新OPTIMUS理论，该公司继续探索具有临床活性的最小剂量，第三个队列已经开始并正在招募。这项试验的初步结果将在6月即将举行的欧洲血液学协会（EHA）2024年大会上公布。。

In addition, in neuroendocrine tumors, in the context of the CRADA agreement between Oryzon and the NIH, the NCI is sponsoring a randomized Phase I/II trial in 1L extensive disease small cell lung cancer combining iadademstat with immune checkpoint inhibitors. The IND for this trial was recently approved by the FDA..

此外，在神经内分泌肿瘤中，在Oryzon和NIH之间的CRADA协议的背景下，NCI正在赞助1L广泛疾病小细胞肺癌的随机I/II期试验，将iadademstat与免疫检查点抑制剂相结合。该试验的IND最近得到了FDA的批准。。

About Oryzon

关于Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego.

Oryzon（ISIN代码：ES0167733015）于2000年在西班牙巴塞罗那成立，是一家临床阶段的生物制药公司，也是欧洲表观遗传学的领导者，专注于中枢神经系统疾病和肿瘤学的个性化医疗。Oryzon的团队由来自巴塞罗那、波士顿和圣地亚哥制药行业的高素质专业人员组成。

Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6, where ORY-4001 has been nominated as clinical candidate for the treatment of certain neurological disorders such as CMT and ALS.

在几项II期临床试验中，Oryzon拥有两种LSD1抑制剂的先进临床组合，即中枢神经系统中的vafidmstat和肿瘤学中的iadademstat。该公司拥有针对其他表观遗传靶标（如HDAC-6）的其他管道资产，其中ORY-4001已被提名为治疗某些神经系统疾病（如CMT和ALS）的临床候选药物。

In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com.

此外，Oryzon为各种恶性和神经疾病的生物标志物鉴定和靶标验证提供了强大的平台。有关更多信息，请访问www.oryzon.com。

About Iadademstat

Iadademstat

Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273.

Iadademstat（ORY-1001）是一种小的口服分子，可作为表观遗传酶LSD1的高选择性抑制剂，在血液系统癌症中具有强大的分化作用（参见Maes等，Cancer Cell 2018 Mar 12；33（3）：495-511.e12.doi:10.1016/j.ccell。2018.02.002）。在R/R AML患者中使用iadademstat进行的FiM I/IIa期临床试验证明了该药物的安全性和良好耐受性以及抗白血病活性的初步迹象，包括CRi（参见Salamero等，J Clin Oncol，2020，38（36）：4260-4273）。

doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and efficacy data in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations.

doi:10.1200/JCO.19.03250）。Iadademstat在老年1L AML患者的IIa期试验（ALICE试验）中与阿扎胞苷联合使用显示出令人鼓舞的安全性和有效性数据（见Salamero等人，ASH 2022口服介绍）。Iadademstat目前正在与吉替尼联合进行正在进行的Ib FRIDA期临床试验，用于FLT3突变的复发/难治性AML患者。

Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster).

除血液系统癌症外，LSD1的抑制已被提议作为一些实体瘤（如小细胞肺癌（SCLC），神经内分泌肿瘤（NET），髓母细胞瘤等）的有效治疗方法。在二线ED-SCLC患者中与铂/依托泊苷联合进行的IIa期试验（CLEPSIDRA试验）中，已经报道了初步的活性和安全性结果（参见Navarro等人，ESMO 2018海报）。

Iadademstat is being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination with immune checkpoint inhibitors (ICI) in SCLC. Oryzon has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S.

Iadademstat正在与Fox Chase癌症中心（FCCC）联合紫杉醇治疗R/R神经内分泌癌的II期篮式合作研究中进行评估，该公司正在准备一项新的试验，与免疫检查点抑制剂（ICI）联合治疗SCLC。Oryzon已与美国签订合作研发协议（CRADA）。

National Cancer Institute (NCI) to collaborate on p.

美国国家癌症研究所（NCI）将在p。

FORWARD-LOOKING STATEMENTS

前瞻性声明

This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance.

本通讯包含或可能包含关于Oryzon的前瞻性信息和声明，包括财务预测和估计及其基本假设，关于未来运营、资本支出、协同效应、产品和服务的计划、目标和期望的声明，以及关于未来业绩的声明。

Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements.

前瞻性陈述是指不是历史事实的陈述，通常用“预期”、“预期”、“相信”、“打算”、“估计”和类似的表达来标识。尽管Oryzon认为这些前瞻性声明中反映的预期是合理的，但投资者和Oryzon股份持有人应注意，前瞻性信息和声明会受到各种风险和不确定性的影响，其中许多风险和不确定性很难预测，并且通常超出Oryzon的控制范围，这可能导致实际结果和发展与前瞻性信息和声明中表达、暗示或预测的结果和发展存在重大差异。

These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon.

这些风险和不确定性包括Oryzon发送给西班牙国家商业价值委员会（CNMV）的文件中讨论或确定的风险和不确定性，公众可以访问这些文件。前瞻性声明并不能保证未来的业绩，也没有经过Oryzon审计师的审查。

You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above.

请注意，不要过度依赖前瞻性声明，这些声明仅在做出之日起生效。所有可归因于Oryzon或其任何成员、董事、高级职员、员工或代表其行事的任何人的后续口头或书面前瞻性声明均明确符合上述警告声明的全部要求。

All forward-loo.

全速前进厕所。

IR, US

IR，美国

IR & Media, Europe

IR&Media，欧洲

Spain

西班牙

Oryzon

稻瘟清

Ashley R. Robinson