LEHI, Utah, Dec. 13, 2023 /PRNewswire/ -- Halia Therapeutics, a clinical-stage biopharmaceutical company pioneering a novel class of small molecule medications designed to combat inflammation, today announced the dosing of the first patient in Phase 2a clinical trial evaluating its lead candidate, HT-6184, for the treatment of lower-risk myelodysplastic syndromes (LR-MDS).

犹他州莱希，2023年12月13日/PRNewswire/-Halia Therapeutics是一家临床阶段生物制药公司，开创了一类旨在对抗炎症的新型小分子药物，今天宣布在2a期临床试验中对第一名患者进行给药，评估其主要候选药物HT-6184，用于治疗低风险骨髓增生异常综合征（LR-MDS）。

HT-6184 is a selective and orally bioavailable first-in-class inhibitor of NLRP3/NEK7 inflammasome, a main driver of inflammatory diseases, as well as hematologic and other malignancies. .

HT-6184是NLRP3/NEK7炎性体的选择性和口服生物可利用的一流抑制剂，NLRP3/NEK7炎性体是炎症性疾病以及血液学和其他恶性肿瘤的主要驱动因素。。

Myelodysplastic syndromes are a group of cancers in which the bone marrow produces underdeveloped (immature) cells that are abnormal in size, shape, or appearance, which are called 'dysplastic. This leads to a reduced number of healthy blood cells, which can result in multiple complications, including but not limited to anemia, recurrent infections, and progression to cancer.

骨髓增生异常综合征是一组癌症，其中骨髓产生大小，形状或外观异常的不发达（未成熟）细胞，称为“发育异常”。这导致健康血细胞数量减少，这可能导致多种并发症，包括但不限于贫血，反复感染和癌症进展。

The trial will evaluate the safety and activity of HT-6184 in up to 40 patients with LR-MDS and will be conducted at multiple sites across India. The study will measure the rate of hematological improvement, including transfusion dependency and changes in hemoglobin levels as primary endpoints for the study.

该试验将评估HT-6184在多达40名LR-MDS患者中的安全性和活性，并将在印度多个地点进行。该研究将测量血液学改善率，包括输血依赖性和血红蛋白水平的变化，作为研究的主要终点。

Secondary endpoints will further assess the effect of HT-6184 on biomarkers of inflammasome activation in MDS and the changes in clone size of somatic gene mutations. The trial is expected to be completed by Q4 2025..

次要终点将进一步评估HT-6184对MDS炎性体激活生物标志物的影响以及体细胞基因突变克隆大小的变化。该试验预计将于2025年第四季度完成。。

'The dosing of the first patient in our Phase 2 trial of HT-6184 marks a significant milestone for Halia in further evaluating the potential of targeting the NLRP3 inflammasome to treat a wide spectrum of immunological and inflammatory diseases,' said Margit M. Janát-Amsbury, MD, Ph.D., Chief Medical Officer of Halia Therapeutics.  'The recent positive results of our Phase I trial investigating HT-6184 are extremely encouraging and highlight the functional activity of HT-6184 in being able to reduce inflammatory cytokines.

“在我们的HT-6184第二阶段试验中，第一名患者的剂量标志着Halia在进一步评估靶向NLRP3炎性体治疗广泛免疫和炎症性疾病的潜力方面的一个重要里程碑，”Margit M。Janát-Amsbury，医学博士，博士，Halia Therapeutics首席医疗官。“我们研究HT-6184的I期试验的最新积极结果非常令人鼓舞，并突出了HT-6184在减少炎性细胞因子方面的功能活性。

As we move into this next stage of clinical testing, we look forward to assessing the potential benefit of our inflammasome inhibitor for MDS patients, as well as for other patients who suffer from inflammation-related diseases.'.

随着我们进入临床测试的下一阶段，我们期待着评估我们的炎性体抑制剂对MDS患者以及其他患有炎症相关疾病的患者的潜在益处。”。

Halia recently announced Phase I trial results evaluating HT-6184, which was shown to be safe, well tolerated and to significantly reduce NLRP3-inflammatory cytokines in healthy volunteers.

Halia最近宣布了评估HT-6184的I期临床试验结果，该试验结果显示HT-6184安全，耐受性良好，并能显着降低健康志愿者的NLRP3炎性细胞因子。

About NLRP3NLRP3, an innate immune sensor, is activated in response to various pathogenic and sterile stimuli. Activation of NLRP3 triggers the release of the pro-inflammatory cytokines IL-1β and IL-18 and induces a lytic cell death process called pyroptosis. These processes lead to systemic chronic inflammation.

关于NLRP3NLRP3，一种先天免疫传感器，被激活以响应各种致病性和无菌刺激。NLRP3的激活触发促炎细胞因子IL-1β和IL-18的释放，并诱导称为pyroptosis的溶解性细胞死亡过程。这些过程导致全身性慢性炎症。

Halia's therapeutic inhibition of NLRP3 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once formed, thereby inhibiting the production and release of IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome is thought to drive the onset and progression of many conditions, including fibrotic, dermatological, and auto-inflammatory diseases.

Halia对NLRP3的治疗性抑制作用可防止NLRP3炎性体的形成，并在形成后促进其分解，从而抑制IL-1β和IL-18的产生和释放。NLRP3炎性体的持续激活被认为可以驱动许多疾病的发作和进展，包括纤维化，皮肤病和自身炎症性疾病。

Significant neurodegenerative and neuroinflammatory disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis are also driven by NLRP3 activation. Notably, in recent years, NLRP3 has been discovered and is gaining significance as one of the key biological drivers of ineffective hematopoiesis and inflammation in MDS..

NLRP3激活也会导致严重的神经退行性疾病和神经炎症性疾病，例如阿尔茨海默氏病，帕金森氏病和多发性硬化症。值得注意的是，近年来，NLRP3已被发现，并且作为MDS中无效造血和炎症的关键生物学驱动因素之一，其意义日益重大。。

About HT-6184HT-6184 represents an innovative approach as it is the first drug candidate to target the protein NEK7 through an allosteric mechanism. NEK7 is an essential component of the NLRP3 inflammasome and is critical for its assembly and the maintenance of NLRP3 activity. In preclinical models, Halia has shown that inhibiting the ability of NEK7 to bind to NLRP3 leads to a disruption in the formation of the NLRP3 inflammasome complex, thereby inhibiting the signaling from the inflammasome and reducing the inflammatory response.

关于HT-6184HT-6184代表了一种创新的方法，因为它是第一个通过变构机制靶向蛋白质NEK7的候选药物。NEK7是NLRP3炎性体的重要组成部分，对其组装和维持NLRP3活性至关重要。在临床前模型中，Halia表明，抑制NEK7与NLRP3结合的能力会导致NLRP3炎性体复合物形成的破坏，从而抑制炎性体的信号传导并减少炎症反应。

Preclinical models also showed that in addition to disrupting the formation of the NLRP3 inflammasome, HT-6184 promotes the disassembly of the inflammasome once activated..

临床前模型还表明，除了破坏NLRP3炎性体的形成外，HT-6184还促进了一旦激活的炎性体的分解。。

About Halia Therapeutics, Inc.Halia Therapeutics is discovering and developing a pipeline of novel therapeutics to improve patients' lives with chronic inflammatory disorders and neurodegenerative diseases, with its initial programs targeting NEK7 and LRRK2. Halia's lead candidate, HT-6184, a novel NEK7/NLRP3 inhibitor, has completed a Phase 1 study (NCT05447546) evaluating the safety and tolerability of HT-6184 when administered as single or multiple oral doses at escalating dose levels in healthy volunteer subjects.

关于Halia Therapeutics，Inc.Halia Therapeutics正在发现和开发一系列新疗法，以改善慢性炎症性疾病和神经退行性疾病患者的生活，其最初的计划针对NEK7和LRRK2。Halia的主要候选药物HT-6184是一种新型NEK7/NLRP3抑制剂，已完成一项1期研究（NCT05447546），评估了HT-6184在健康志愿者受试者中以递增剂量水平单次或多次口服给药时的安全性和耐受性。

The company is headquartered in Lehi, Utah. For more info, visit www.haliatx.com or follow us on LinkedIn and Twitter (X)..

该公司总部位于犹他州莱希。欲了解更多信息，请访问www.haliatx.com或在LinkedIn和Twitter（X）上关注我们。。

Company Contact: James Dye+1.385.355.4315[email protected]

公司联系人：James Dye+1.385.355.4315[受电子邮件保护]

Media Contact:Ignacio Guerrero-Ros, Ph.D.Russo Partners, LLC+1 (646) 942-5604[email protected]

媒体联系人：Ignacio Guerrero Ros，Ph.D.Russo Partners，LLC+1（646）942-5604[受电子邮件保护]

SOURCE Halia Therapeutics

来源Halia Therapeutics