英矽智能自研口服小分子ISM5939获美国FDA临床试验批件

● 在英矽智能自主开发的30余条AI驱动药物管线中，ISM5939是第10个获得IND批件的创新分子 

● 英矽智能利用专有Pharma.AI平台下属生成式AI引擎，实现ISM5939早期开发加速，在项目启动3个月内高效获得了先导化合物 

马萨诸塞州剑桥市，2024年11月21日 --- 全球领先由生成式AI驱动的生物科技公司英矽智能宣布，公司自研潜在“同类最佳”（best-in-class）ENPP1口服小分子抑制剂已经获得美国食品药品监督管理局（FDA）的IND批件，用于实体瘤治疗。至此，英矽智能以生成式AI为驱动进行自主研发，并成功获得临床试验批件的分子数量达到10个。 

ENPP1是一种外核苷酸焦磷酸酶，在调节免疫、心血管、神经系统、组织矿化和血液系统功能的嘌呤信号传导中发挥重要作用，ENPP1高表达与肿瘤转移、免疫逃逸、多癌种较差预后相关。研究结果显示，ENPP1抑制剂可通过调节胞外cGAMP水平激活cGAS-STING通路，进而增强宿主免疫系统抗肿瘤效果。 

2023年5月，英矽智能宣布提名ISM5939作为临床前候选化合物（PCC），靶向ENPP1潜在用于癌症免疫疗法研发。根据临床前数据，ISM5939在体内研究中展现出强大的抗肿瘤效果，同时显示出良好的安全性特征、体外ADMET特征和体内药代动力学（PK）特征。 

英矽智能首席医学官Sujata Rao表示：“我对ISM5939的临床应用潜力抱有高度期待。在临床前实验中，该候选药物展现出广泛的安全窗和优异的联合治疗潜力，我们期待它可以显著扩展肿瘤患者的治疗选择。” 

基于英矽智能自有Pharma.AI平台旗下生成化学引擎Chemistry42，公司药物化学团队开展进一步分子优化，最终在项目启动3个月内就获得具有新颖分子骨架的先导化合物。 

英矽智能联合首席执行官兼首席科学官任峰博士表示：“AI制药行业需要真实世界的应用案例来完成概念验证。在英矽智能，我们以持续不断的在研项目里程碑，印证公司专有AI平台的潜力，迄今为止已有10款AI赋能研发的候选药物获得IND批件。我们期待在临床阶段进一步验证自研管线、稳步推进AI驱动的药物研发，为全球患者谋福祉。” 

●  Among the 30+ AI-driven pipelines self-developed by Insilico, ISM5939 marks the 10th molecule to receive IND clearance.  

● Insilico utilized proprietary generative AI engines affiliated to Pharma.AI to accelerate the early development of ISM5939, obtaining the lead compound within 3 months of project initiation. 

CAMBRIDGE, Mass., Nov 21, 2024 --- Insilico Medicine (“Insilico”), a clinical-stage generative artificial intelligence (AI)-driven drug discovery company, announced that it has received IND clearance from FDA for ISM5939, a potential best-in-class oral small molecule inhibitor targeting ENPP1 for the treatment of solid tumors. The achievement marks the 10th AI-driven molecule self-developed by Insilico to be recognized with clearance to enter clinical trials. 

ENPP1 is an ecto-nucleotide pyrophosphatase that plays an important role in purinergic signaling that regulates immune, cardiovascular, neurological, and hematological system functions. Elevated ENPP1 expression is associated with metastasis and poor prognosis in multiple tumor types. ENPP1 inhibition enhances the anti-tumor effect of the host immune system by regulating extracellular cGAMP levels to activate the cGAS-STING pathway. 

In May 2023, Insilico Medicine announced the nomination of ISM5939 as a preclinical candidate compound (PCC) targeting ENPP1, with the potential for cancer immunotherapy. According to preclinical data, ISM5939 demonstrated robust anti-tumor efficacy in in vivo studies, while showing favorable safety profile, as well as in vitro ADMET and in vivo pharmacokinetic profiles. 

"I am looking forward to the forthcoming clinical signal of ISM5939." says Sujata Rao, M.D., Chief Medical Officer of Insilico Medicine. "With its favorable safety window and high potential for combination therapy, it is poised to significantly broaden the spectrum of treatment options for cancer patients." 

Powered by Chemistry42, Insilico's proprietary generative chemistry engine affiliated to Pharma.AI, Insilico obtained the lead compound with a distinctly novel molecular structure within 3 months of project initiation, after dedicated optimization through structural modifications by Insilico's medicinal chemists. 

"The AI-driven drug discovery industry requires real-world proof-of-concept cases. At Insilico, we have showcased the potential of our proprietary AI platform through consistent milestones in our ongoing pipeline, with 10 AI-enabled drug candidates successfully obtaining IND approvals to date." says Feng Ren, Ph.D., Co-CEO and Chief Scientific Officer of Insilico Medicine. "We are eager to further validate the company’s in-house R&D pipeline in the clinical stage and to continue advancing AI-powered drug discovery and development for the benefit of patients worldwide."

In 2016, Insilico first described the concept of using generative AI for the design of novel molecules in a peer-reviewed journal, which laid the foundation for the commercially available Pharma.AI platform. Since then, Insilico keeps integrating technical breakthroughs into Pharma.AI platform, which is currently a generative AI-powered solution spanning across biology, chemistry, medicine development and science research. Powered by Pharma.AI, Insilico has nominated 20 preclinical candidates in its comprehensive portfolio of over 30 assets since 2021 and has received IND clearance for 10 molecules. 

In early 2024, Insilico published a Nature Biotechnology paper presenting the entire R&D journey from AI algorithms to Phase II clinical trials of ISM001_055, the company's lead drug pipeline with AI-discovered target and AI-designed structure. Following that, Insilico has recently announced positive preliminary results from a Phase IIa trial (NCT05938920), where ISM001_055 showed favorable safety and tolerability across all dose levels, as well as dose-dependent response in forced vital capacity (FVC), after only 12 weeks of dosage.