BOSTON--(BUSINESS WIRE)--Nimbus Therapeutics, LLC ('Nimbus Therapeutics' or 'Nimbus'), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, today announced the presentation of new clinical and translational data from its ongoing Phase 1/2 trial of NDI-101150, a novel, oral, potent and selective small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, for the treatment of advanced solid tumors.

波士顿--（商业新闻短讯）--Nimbus Therapeutics，LLC（“Nimbus Therapeutics”或“Nimbus”）是一家生物技术公司，通过其强大的计算药物发现引擎为患者设计和开发突破性药物，今天宣布展示其正在进行的NDI-101150（一种新型，口服，有效和选择性的小分子造血祖细胞激酶1（HPK1）抑制剂）1/2期临床试验的新临床和翻译数据，用于治疗晚期实体瘤。

Results will be highlighted in two poster presentations at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, taking place November 6-10, 2024 in Houston, Texas..

2024年11月6日至10日在德克萨斯州休斯顿举行的癌症免疫治疗学会（SITC）第39届年会上，两张海报将突出显示研究结果。。

The Phase 1/2 multicenter, open-label trial (NCT05128487) is designed to assess NDI-101150 as a monotherapy (50-200 mg QD dose) and in combination with pembrolizumab (200 mg Q3W) in the treatment of adults with advanced solid tumors. The clinical results being presented at the SITC Annual Meeting include updated safety data from 53 patients in the dose escalation cohorts (n=41 on monotherapy, n=12 on combination therapy) and additional data from 35 patients in the dose expansion cohorts as well as updated efficacy data from 17 response-evaluable patients with renal cell carcinoma (RCC) who received NDI-101150 monotherapy.

1/2期多中心开放标签试验（NCT05128487）旨在评估NDI-101150作为单一疗法（50-200 mg QD剂量），并与pembrolizumab（200 mg Q3W）联合治疗成人晚期实体瘤。在SITC年会上公布的临床结果包括来自剂量递增队列中53名患者的最新安全性数据（单药治疗n=41，联合治疗n=12）和来自剂量扩展队列中35名患者的额外数据以及来自17名接受NDI-101150单药治疗的可反应评估肾细胞癌（RCC）患者的最新疗效数据。

Results, as of August 12, 2024, showed:.

截至2024年8月12日，结果显示：。

Safety Profile

安全简介

NDI-101150 was generally well-tolerated with immune-related adverse events supporting the proposed mechanism of action of HPK1 inhibition, which results in immune activation.

NDI-101150通常具有良好的耐受性，与免疫相关的不良事件支持所提出的HPK1抑制作用机制，从而导致免疫激活。

Grade ≥3 treatment-related adverse events (TRAEs) occurred in 14% of all patients exposed to NDI-101150 (n=88). The most common TRAEs were nausea, diarrhea, vomiting and fatigue.

暴露于NDI-101150（n=88）的所有患者中有14%发生≥3级治疗相关不良事件（TRAEs）。最常见的TRAE是恶心，腹泻，呕吐和疲劳。

Efficacy and Target Engagement

功效和目标参与

Treatment with NDI-101150 monotherapy resulted in objective responses in 18% (3/17) of response-evaluable RCC patients, including one complete response (CR) and two partial responses (PRs).

NDI-101150单药治疗在18%（3/17）的可评估反应的RCC患者中产生了客观反应，包括一个完全反应（CR）和两个部分反应（PR）。

A clinical benefit rate (CR + PR + stable disease [SD] ≥6 months) of 29% (5/17) and a disease control rate of 65% (11/17) were observed in response-evaluable RCC patients treated with NDI-101150 monotherapy.

在用NDI-101150单药治疗的可评估反应的RCC患者中，观察到临床获益率（CR+PR+稳定疾病[SD]≥6个月）为29%（5/17），疾病控制率为65%（11/17）。

NDI-101150 effectively inhibited its target across multiple dose levels, providing strong pharmacodynamic evidence of the molecule's activity in patients.

NDI-101150在多个剂量水平上有效抑制其靶标，为该分子在患者中的活性提供了强有力的药效学证据。

Supporting Mechanistic Evidence

支持机械证据

Analysis of tumor biopsies showed a more robust presence of immune cells post-treatment, with increased numbers of tumor-infiltrating lymphocytes and dendritic cells in the tumor microenvironment.

对肿瘤活检的分析显示，治疗后免疫细胞的存在更加强烈，肿瘤微环境中肿瘤浸润淋巴细胞和树突状细胞的数量增加。

Comprehensive gene expression profiling demonstrated broad activation of immune-related pathways, including enhanced interferon response and T cell activation signals.

全面的基因表达谱显示免疫相关途径的广泛激活，包括增强的干扰素应答和T细胞活化信号。

'These clinical results of NDI-101150 are highly encouraging, particularly in the context of renal cell carcinoma patients who have experienced disease progression on prior checkpoint inhibitors,' said Nathalie Franchimont, M.D., Ph.D., Chief Medical Officer of Nimbus. 'The objective responses and disease control rates seen thus far with NDI-101150 in heavily pretreated patients as well as the current safety profile support further evaluation of NDI-101150 in the clinic.'.

Nimbus首席医疗官Nathalie Franchimont医学博士说：“NDI-101150的这些临床结果非常令人鼓舞，特别是在肾细胞癌患者中，他们在先前的检查点抑制剂上经历了疾病进展。”迄今为止，NDI-101150在经过严重预处理的患者中的客观反应和疾病控制率以及目前的安全性概况支持在临床上进一步评估NDI-101150。”。

'The clinical and translational data package being presented at SITC demonstrates both the therapeutic potential of NDI-101150 and the power of our computational drug discovery engine to design highly selective molecules against challenging targets like HPK1,' said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus.

Nimbus首席执行官、工商管理硕士杰布·凯珀（JebKeiper）说：“在SITC上展示的临床和翻译数据包既展示了NDI-101150的治疗潜力，也展示了我们的计算药物发现引擎设计针对HPK1等具有挑战性目标的高选择性分子的能力。”。

'The monotherapy activity we observed is particularly noteworthy, as many second-generation immunotherapy compounds have struggled to show clinical benefit on their own. Together with its safety profile and the immune activation signals we've observed, these data support NDI-101150's potential as a novel oral non-checkpoint immunotherapy option for patients who need new treatment approaches beyond current checkpoint inhibitors.'.

“我们观察到的单一疗法活性特别值得注意，因为许多第二代免疫治疗化合物一直在努力显示其自身的临床益处。结合其安全性和我们观察到的免疫激活信号，这些数据支持NDI-101150作为一种新型口服非检查点免疫治疗选择的潜力，适用于需要超越当前检查点抑制剂的新治疗方法的患者。”。

The abstracts are available in the Journal for ImmunoTherapy of Cancer (JITC), the official journal of SITC, here and the details of the poster presentations are as follows:

摘要可在《癌症免疫治疗杂志》（JITC）（SITC的官方杂志）上找到，海报展示的细节如下：

Title: Ongoing Phase 1/2 Trial of the HPK1 Inhibitor NDI-101150 as Monotherapy and in Combination with Pembrolizumab: Clinical Safety Update and Renal Cell Carcinoma (RCC) Efficacy Analysis

标题：HPK1抑制剂NDI-101150作为单一疗法并与Pembrolizumab联合进行的1/2期临床试验：临床安全性更新和肾细胞癌（RCC）疗效分析

Lead Author: David Sommerhalder, M.D., Director of Clinical Research, NEXT Oncology

主要作者：David Sommerhalder，医学博士，NEXT肿瘤学临床研究主任

Date: Saturday, November 9, 2024

日期：2024年11月9日，星期六

Time: 9:00 a.m. – 8:30 p.m. CST

Time: 9:00 a.m. – 8:30 p.m. CST

Category: Clinical Trials in Progress

类别：正在进行的临床试验

Abstract Number: 682

摘要编号：682

Title: Tumor Immune Microenvironment Characterization from Pre- and Post-Dose Tumors Collected from a Phase 1/2 Study of NDI-101150, a Hematopoietic Progenitor Kinase 1 (HPK1) inhibitor

标题：从造血祖细胞激酶1（HPK1）抑制剂NDI-101150的1/2期研究中收集的剂量前后肿瘤的肿瘤免疫微环境表征

Lead Author: Scott Daigle, Senior Director, Translational Medicine, Nimbus Therapeutics

主要作者：ScottDaigle，Nimbus Therapeutics转化医学高级总监

Date: Friday, November 8, 2024

日期：2024年11月8日，星期五

Time: 9:00 a.m. – 7:00 p.m. CST

Time: 9:00 a.m. – 7:00 p.m. CST

Category: Biomarkers, Immune Monitoring and Novel Technologies

类别：生物标志物，免疫监测和新技术

Abstract Number: 83

摘要编号：83

About Nimbus Therapeutics

关于Nimbus Therapeutics

Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches.

Nimbus Therapeutics是一家临床阶段，基于结构的药物发现公司，开发新型小分子药物，旨在对抗多种人类疾病中经过充分验证但难以药物靶点。该公司基于独特的策略推进了有前景的研究，该策略将前沿计算技术与定制的基于机器学习的预测建模方法相结合。

Nimbus' pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, including a WRN program for MSI-H cancers, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass.

Nimbus的管道包括用于治疗癌症的临床阶段HPK1抑制剂（NCT05128487），以及针对癌症的多种临床前计划，包括针对MSI-H癌症，自身免疫性疾病和代谢性疾病的WRN计划。。

To learn more about Nimbus, please visit www.nimbustx.com..

要了解有关Nimbus的更多信息，请访问www.nimbustx.com。。