MRT-8102 nominated as first NEK7-directed development candidate, targeting inflammatory diseases driven by IL-1βand the NLRP3 inflammasome

MRT-8102被提名为第一个NEK7定向发育候选者，靶向由IL-1β和NLRP3炎性体驱动的炎症性疾病

MRT-8102 and other NEK7 program MGDs are potentially applicable across a range of inflammatory disorders, metabolic disorders, as well as ocular and neurological diseases

MRT-8102和其他NEK7程序MGD可能适用于一系列炎症性疾病，代谢性疾病以及眼部和神经系统疾病

IND-enabling studies ongoing; IND submission anticipated in Q1 2025

IND使能研究正在进行中；预计2025年第一季度提交IND

BOSTON, March 11, 2024 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced a novel development candidate, MRT-8102, a potent, highly selective and orally bioavailable NIMA related kinase 7 (NEK7)-directed MGD.

波士顿，2024年3月11日（环球通讯社）--Monte Rosa Therapeutics，Inc.（纳斯达克：GLUE），一家开发新型分子胶降解剂（MGD）药物的临床阶段生物技术公司，今天宣布了一种新的开发候选药物MRT-8102，一种有效的，高选择性和口服生物可利用的NIMA相关激酶7（NEK7）指导的MGD。

MRT-8102 is expected to be developed for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, which are critical elements of the inflammatory process. This is the first development candidate to be declared from the Company’s NEK7 development program..

预计将开发MRT-8102用于治疗由白细胞介素-1β（IL-1β）和NLRP3炎性体驱动的炎症性疾病，这是炎症过程的关键因素。这是该公司NEK7开发计划中宣布的第一个开发候选人。。

“NEK7 is an essential component of the NLRP3 inflammasome pathway that has been implicated in many serious diseases, and we are excited to advance MRT-8102 toward clinical development,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “In preclinical non-human primate studies, MRT-8102 has demonstrated potent and selective degradation of NEK7, reducing downstream IL-1β.

Monte Rosa Therapeutics首席执行官Markus Warmuth医学博士说：“NEK7是NLRP3炎性体途径的重要组成部分，与许多严重疾病有关，我们很高兴将MRT-8102推向临床开发。”。“在临床前非人类灵长类动物研究中，MRT-8102已证明NEK7具有有效和选择性的降解作用，从而降低了下游IL-1β。

We believe MRT-8102 has the potential to be developed in multiple inflammatory diseases, including gout, pericarditis and other cardiovascular diseases. We are also evaluating opportunities for the program in CNS disorders such as Parkinson’s disease as well as in obesity and other metabolic disorders in light of the ability of our NEK7-directed MGDs to penetrate the blood brain barrier.

我们相信MRT-8102有可能在多种炎症性疾病中发展，包括痛风，心包炎和其他心血管疾病。鉴于我们的NEK7定向MGD穿透血脑屏障的能力，我们还在评估该计划在中枢神经系统疾病（如帕金森氏病）以及肥胖和其他代谢紊乱中的机会。

IND-enabling studies are underway, and we plan to file our first IND for the program in the first quarter of 2025. The advancement of MRT-8102, along with our VAV1-directed MGD MRT-6160, which is progressing toward an IND filing in the first half of this year, demonstrates the continued growth of our immunology and inflammation portfolio and the power and versatility of our QuEEN™ discovery engine.”.

支持IND的研究正在进行中，我们计划在2025年第一季度为该计划提交第一份IND。MRT-8102的进步，以及我们针对VAV1的MGD MRT-6160，正朝着今年上半年的IND申请迈进，证明了我们的免疫学和炎症组合的持续增长以及我们QuEEN™发现引擎的力量和多功能性。”。

The NLRP3 inflammasome is a multiprotein complex that regulates the innate immune system and inflammatory signaling. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurological disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease.

NLRP3炎性体是一种多蛋白复合物，可调节先天免疫系统和炎症信号传导。异常的NLRP3炎性体激活和随后释放的活性IL-1β和白细胞介素-18（IL-18）与多种炎症性疾病有关，包括痛风，心血管疾病，包括帕金森病和阿尔茨海默病在内的神经系统疾病，眼部疾病，糖尿病，肥胖和肝病。

NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo, and Monte Rosa’s own in vitro and in vivo work has shown that NEK7 degradation leads to blockade of the pathway leading to inhibition of the production of IL-1β..

NEK7已被证明是NLRP3炎性体组装，激活和IL-1β释放在体外和体内所必需的，Monte Rosa自己的体外和体内工作表明，NEK7降解导致阻断导致抑制IL-1β产生的途径。。

About MRT-8102

关于MRT-8102

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NRLP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo.

MRT-8102是一种有效的，高选择性和口服生物可利用的研究性分子胶降解剂（MGD），其靶向NEK7以治疗由IL-1β和NRLP3炎性体驱动的炎性疾病。已显示NEK7是体外和体内NLRP3炎性体组装，激活和IL-1β释放所必需的。

Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurological disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease.

异常的NLRP3炎性体激活和随后释放的活性IL-1β和白细胞介素-18（IL-18）与多种炎症性疾病有关，包括痛风，心血管疾病，包括帕金森病和阿尔茨海默病在内的神经系统疾病，眼部疾病，糖尿病，肥胖和肝病。

In non-human primate models, MRT-8102 potently, selectively, and durably degrades NEK7 and results in near-complete reductions of IL-1β. MRT-8102 has shown a favorable safety profile in non-GLP toxicology studies..

在非人灵长类动物模型中，MRT-8102有效，选择性和持久地降解NEK7，并导致IL-1β几乎完全降低。MRT-8102在非GLP毒理学研究中显示出良好的安全性。。

About Monte Rosa

关于Monte Rosa

Monte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot.

Monte Rosa Therapeutics是一家临床阶段的生物技术公司，为肿瘤学，自身免疫性和炎症性疾病等领域的严重疾病患者开发高选择性分子胶降解剂（MGD）药物。MGD是小分子蛋白质降解剂，有可能治疗许多其他方式（包括其他降解剂）无法治疗的疾病。

Monte Rosa’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology and proteomics to identify degradable protein targets and rationally design MGDs with unprecedented selectivity. The QuEEN discovery engine enables access to a wide-ranging and differentiated target space of well-validated biology across multiple therapeutic areas.

Monte Rosa的QuEEN™（新底物的定量和工程消除）发现引擎结合了AI指导的化学，多种化学文库，结构生物学和蛋白质组学，以鉴定可降解的蛋白质靶标，并以前所未有的选择性合理设计MGD。QuEEN discovery引擎可以在多个治疗领域访问经过充分验证的生物学的广泛且差异化的目标空间。

Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans oncology, autoimmune and inflammatory disease and beyond, and has a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug.

Monte Rosa开发了业界领先的MGD管道，涵盖肿瘤学，自身免疫性和炎症性疾病等领域，并与罗氏公司进行了战略合作，以发现和开发针对癌症和神经系统疾病的MGD，这些疾病以前被认为是不可能药物治疗的。

For more information, visit www.monterosatx.com..

有关更多信息，请访问www.monterosatx.com。。

Forward-Looking Statements

前瞻性声明

This communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future.

该通信包括明示和暗示的“前瞻性声明”，包括1995年《私人证券诉讼改革法案》所指的前瞻性声明。前瞻性陈述包括所有非历史事实的陈述，在某些情况下，可以通过“可能”、“可能”、“将会”、“可能”、“将会”、“应该”、“预期”、“打算”、“计划”、“目标”、“预期”、“相信”、“估计”、“预测”、“潜在”、“继续”、“持续”等术语来识别或这些术语的否定词，或旨在识别未来陈述的其他类似术语。

Forward-looking statements contained herein include, but are not limited to, statements about the ongoing development of our NEK7 program, including our MGDs and product candidates therein, including our recently announced product candidate MRT-8102, our ability to generate additional product candidates for our NEK7 program, the therapeutic potential of NEK7 MGDs, including MRT-8102, including for the treatment of inflammatory diseases driven by IL-1β and the NRLP3 inflammasome, our expectations regarding the submission of any IND to the FDA for each of MRT-8102 and MRT-6160 and the timing thereof, our expectations of the nature and timing for clinical advancement for MRT-8102, and our expectations regarding the potential clinical benefit for this program.

本文包含的前瞻性声明包括但不限于关于我们NEK7计划正在进行的开发的声明，包括我们的MGD和其中的候选产品，包括我们最近宣布的候选产品MRT-8102，我们为NEK7计划生成其他候选产品的能力，NEK7 MGD的治疗潜力，包括MRT-8102，包括治疗由IL-1β和NRLP3炎性体驱动的炎症性疾病，我们对MRT-8102和MRT-6160各自向FDA提交任何IND及其时间的期望，我们对MRT-8102临床进展的性质和时间的期望，以及我们对该计划潜在临床益处的期望。

By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission on March 16, 2023, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely fro.

就其性质而言，这些报表存在许多风险和不确定性，包括我们于2023年3月16日向美国证券交易委员会提交的截至2023年12月31日的10-K表最新年度报告中规定的风险和不确定性，以及可能导致实际结果的任何后续文件，表现或成就存在重大不利差异。

Investors

投资者

Andrew Funderburk

安德鲁·芬德布鲁克

ir@monterosatx.com

ir@monterosatx.com

Media

媒体

Cory Tromblee, Scient PR

Cory Tromblee，科学公关

media@monterosatx.com

media@monterosatx.com