CAMBRIDGE, Mass.--(BUSINESS WIRE)--Exo Therapeutics, Inc., a company developing a pipeline of drug candidates that target exosites, unique small-molecule binding pockets that are distal to traditional active and allosteric sites, thereby reprogramming enzyme activity for precise and robust therapeutic effect, today presented a poster and oral presentation on its preclinical program targeting TBK1/STING interaction of the cGAS-STING pathway at the 24th Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS 2024) in San Francisco..

马萨诸塞州剑桥市。-（商业新闻短讯）--Exo Therapeutics，Inc.，一家开发候选药物管道的公司，该候选药物靶向外显子，独特的小分子结合口袋，远离传统的活性和变构位点，从而重新编程酶活性以获得精确和强大的治疗效果，今天在旧金山举行的临床免疫学会联合会（FOCIS 2024）第24届年会上，针对其针对cGAS-STING途径的TBK1/STING相互作用的临床前计划进行了海报和口头介绍。。

Data presented in both the poster and oral presentation show that the company has identified potent, selective exosite-targeted TBK1/STING inhibitors, demonstrated efficacy across preclinical models and optimized properties towards development candidate nomination. FOCIS also recognized Exo with the 2024 Annual Meeting Award for exceptional research and posters of merit for the Company’s poster and oral presentation..

海报和口头演示中提供的数据表明，该公司已经确定了有效的，选择性的外位点靶向TBK1/STING抑制剂，在临床前模型中表现出功效，并优化了开发候选人提名的特性。FOCIS还授予Exo 2024年年度会议杰出研究奖，以及公司海报和口头展示的优秀海报。。

“Exo’s data look very promising, particularly the targeting of both interferon-beta and NF-kB pathways by your molecule,” said Mary K. Crow, M.D., Physician-in-Chief Emeritus at Hospital for Special Surgery and Professor of Medicine at Weill Cornell Medical College. “There is a great need to define the role of the TBK1/STING pathway in Systemic Lupus Erythematosus (SLE) and other autoimmune diseases.

“Exo的数据看起来非常有希望，特别是通过你的分子靶向干扰素-β和NF-κB途径，”医学博士玛丽·克劳（MaryK.Crow）说，她是特殊外科医院的名誉主治医师，也是威尔·康奈尔医学院的医学教授。“非常需要确定TBK1/STING途径在系统性红斑狼疮（SLE）和其他自身免疫性疾病中的作用。

I hope Exo’s development program can soon move forward into patients with their interesting drug!”.

我希望Exo的开发计划能够很快进入患者的有趣药物！”。

Exo’s goal is to expand the druggable universe with exosite-specific molecules that enable a new, tailored way to target and reprogram enzymes. Historically, active-site inhibitors have failed because of inadequate selectivity of their inhibitory activity, leading to off-target effects and poor therapeutic indices.

Exo的目标是用外源特异性分子扩大可药用范围，从而实现一种新的定制方式来靶向和重新编程酶。历史上，活性位点抑制剂由于其抑制活性的选择性不足而失败，导致脱靶效应和较差的治疗指数。

Moreover, molecules focused on active or allosteric sites typically inhibit the full functionality of proteins, which can direct both beneficial and harmful effects. In contrast, TBK1/STING exosite inhibitors have the promise of mitigating the unwanted effects while providing therapeutic benefit..

此外，专注于活性或变构位点的分子通常会抑制蛋白质的全部功能，这可以指导有益和有害的作用。相反，TBK1/STING外位点抑制剂有望减轻不良反应，同时提供治疗益处。。

The presentations detailed Exo’s novel TBK1 exosite inhibitors that disrupt recruitment by STING for downstream activation of type-1 interferon and NF-κB responses. More specifically, TBK1 exosite inhibitors selectively inhibit the TBK1-STING axis while sparing non-disease relevant housekeeping functions of the kinase, which will be more likely to offer superior efficacy and an improved therapeutic window versus traditional approaches.

演讲详细介绍了Exo的新型TBK1外位点抑制剂，该抑制剂通过STING破坏募集，从而下游激活1型干扰素和NF-κB反应。更具体地说，TBK1外位点抑制剂选择性地抑制TBK1-STING轴，同时保留激酶的非疾病相关管家功能，与传统方法相比，这更有可能提供优异的疗效和改进的治疗窗口。

The company also shared findings from rational and structure-based drug discovery efforts that demonstrated identification of a series of selective TBK1 exosite inhibitors with potent binding affinities that translate into nanomolar inhibition of IFNβ in THP1 cells and primary human cell types..

。。

Additionally, orally bioavailable TBK1 exosite inhibitors were evaluated in both in vivo and ex vivo models to inhibit proximal and distal pharmacodynamic markers upon stimulation with a STING agonist. Treatment with TBK1 exosite inhibitors caused a dramatic reduction of pro-inflammatory cytokines including IFNβ, CXCL-10, CXCL-9 and IFIT1 in a pathway-driven model, the TREX-1 null mouse.

另外，在体内和离体模型中评估口服生物可利用的TBK1外位点抑制剂，以在用STING激动剂刺激后抑制近端和远端药效学标记。在途径驱动的模型TREX-1无效小鼠中，用TBK1外位点抑制剂治疗导致促炎细胞因子（包括IFNβ，CXCL-10，CXCL-9和IFIT1）的显着减少。

Additionally, Exo’s TBK1 exosite inhibitors have shown robust effects in SLE and Scleroderma patient samples..

此外，Exo的TBK1外位点抑制剂在SLE和硬皮病患者样本中显示出强大的作用。。

Most notably, when assessed for activity in SLE patient-derived human whole blood and PBMC, TBK1 exosite inhibitors robustly suppressed pathway activation. Similarly, upon activation of cGAS-STING-TBK1 pathway, TBK1 exosite inhibitors inhibited cytokine production in disease-relevant skin inflammatory models, fibroblasts and keratinocytes..

最值得注意的是，当评估SLE患者来源的人全血和PBMC的活性时，TBK1外位点抑制剂强烈抑制了途径激活。类似地，在激活cGAS-STING-TBK1途径后，TBK1外位点抑制剂抑制疾病相关皮肤炎症模型，成纤维细胞和角质形成细胞中细胞因子的产生。。

Poster Details

海报详细信息

Title: A Novel Inhibitor of cGAS-STING-TBK1 Pathway with Broad Application in Autoimmune Diseases

标题：一种新型cGAS-STING-TBK1通路抑制剂，在自身免疫性疾病中有广泛应用

Date: Wednesday, June 19, 2024, 7:30 AM - 7:30 PM

日期：2024年6月19日，星期三，上午7:30-下午7:30

Poster Number: W102

海报编号：W102

Location: San Francisco Marriott Marquis – Salon 9, Lower B2 Level

地点：旧金山马奎斯万豪酒店——9号沙龙，B2层下层

Oral Presentation Details

口头演示详细信息

Title: A Novel Inhibitor of cGAS-STING-TBK1 Pathway with Broad Application in Autoimmune Diseases

标题：一种新型cGAS-STING-TBK1通路抑制剂，在自身免疫性疾病中有广泛应用

Date: Wednesday, June 19, 2024, 4:15 PM - 4:30 PM

日期：2024年6月19日星期三下午4:15-下午4:30

Presenter: Bhavatarini Vangamudi, Ph.D.

出席者：Bhavatarini Vangamudi博士。

About Exo Therapeutics

关于Exo Therapeutics

Exo Therapeutics is a small molecule drug discovery and development company co-founded by Professors David R. Liu, Alan Saghatelian, and Juan Pablo Maianti with a pioneering technology to address intractable pharmaceutical targets. By leveraging the company’s ExoSight™ platform, Exo is developing a deep pipeline of potent drug candidates that bind exosites, distal and unique binding pockets that have the potential to reprogram enzyme activity for precise and robust therapeutic effect.

Exo Therapeutics是一家小分子药物发现和开发公司，由David R.Liu教授，Alan Saghatelian教授和Juan Pablo Maianti教授共同创立，拥有解决棘手药物靶标的开创性技术。。

Through this specific and selective approach to challenging targets, the company's team of world-class researchers is unlocking breakthrough therapeutics in inflammation, oncology and a broad range of other diseases. For more information, visit www.exo-therapeutics.com..

。有关更多信息，请访问www.exo-therapeutics.com。。