AI-powered CKD drug ISM4808 licensed for kidney disease therapy

Insilico Medicine, a clinical-stage company specialising in generative artificial intelligence (AI) for drug discovery, has entered an exclusive pipeline out-licensing collaboration with TaiGen Biotechnology and its wholly owned Beijing subsidiary, TaiGen Biopharmaceuticals. The agreement grants TaiGen exclusive rights to develop, commercialise and sub-license ISM4808, a PHD inhibitor, across the Greater China region.

The discovery and development journey of the ISM4808 series was published in the Journal of Medicinal Chemistry.

Targeting a critical clinical need

Chronic kidney disease (CKD) contributes to over 1.5 million deaths annually. More than one in seven CKD patients develop anaemia, often due to reduced levels of erythropoietin (EPO) – a hormone that stimulates bone marrow to produce red blood cells – and shorter red blood cell lifespans. Current treatments focus primarily on symptom relief, including fatigue, shortness of breath, body aches and dizziness, rather than offering a complete cure.

ISM4808, nominated in 2022 as a potential best-in-class PHD inhibitor, targets the Nobel Prize-winning HIF‑α pathway. By inducing EPO production and improving iron utilisation, the molecule aims to enhance red blood cell replacement in CKD-related anaemia. The novel structure of ISM4808 was developed using Insilico’s Chemistry42 engine and was designed, synthesised and tested within 12 months prior to candidate nomination.

“We are delighted to collaborate with Taigen Biotech. Powered by AI, Insilico has efficiently nominated two novel PHD inhibitors for different indications. ISM5411, a gut-restricted molecule for inflammatory bowel disease, has completed two Phase I trials, and demonstrated a favourable safety profile, further strengthened our confidence in PHD-targeting programs,” said Dr Feng Ren, co-CEO and CSO of Insilico Medicine.

Strong preclinical data

Preclinical studies of ISM4808 have demonstrated potency in both in vitro and in vivo assays, with lower effective doses observed in CKD rat models. The molecule exhibited oral drug-like properties, including favourable in vitro ADME characteristics and promising pharmacokinetic profiles across animal models. Safety assessments also indicated high maximum tolerated doses and broad safety margins.

Looking ahead

The collaboration marks a significant milestone in the integration of AI-driven drug discovery with established pharmaceutical development expertise. By combining Insilico’s rapid discovery capabilities with TaiGen’s clinical and commercial resources, ISM4808 could become a transformative treatment option for CKD-related anaemia.

 “As oral drugs progressively replace traditional injectables, TaiGen is dedicated to advancing this innovative program to meet the urgent clinical need for convenient and compliant therapies,” said Kuo-Lung Huang, Chairman of TaiGen Biotechnology.