Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor

HIF-PHD Inhibitor

ISM-4808

Overview Superiority Marketplace Development

Overview

Anemia in Chronic Kidney Disease (CKD Anemia) represents a significant global healthcare challenge. Statistics indicate that complications related to CKD lead to more than 1.5 million deaths annually worldwide. In 2023, the dialysis population in Mainland China surpassed one million and continues to grow at a CAGR of 12.8% (2012–2023), reflecting a structural upward trend in demand for end-stage renal disease (ESRD) treatments. The prevalence of CKD anemia increases as the disease progresses, affecting approximately 20% of patients in Stage 3 and rising to over 90% in Stage 5.

Clinical Needs and Therapeutic Bottlenecks Due to declining renal function, CKD patients suffer from insufficient secretion of endogenous erythropoietin (EPO), resulting in inadequate red blood cell production. Current standard-of-care primarily involves Erythropoiesis-Stimulating Agent (ESA) injections. While these reduce symptoms, significant unmet medical needs remain, including the inconvenience of injections, ESA hyporesponsiveness or intolerance, and poor response in patients with high levels of inflammation.

ISM-4808: Pregulating Physiological Response to Promote Erythropoiesis ISM-4808 is a Hypoxia-Inducible Factor Prolyl Hydroxylase (HIF-PHD) inhibitor. Its mechanism of action is based on the Nobel Prize-winning HIF-α signaling pathway. By inhibiting the PHD enzyme, the drug mimics the body’s physiological response to hypoxia (low oxygen), thereby stimulating the production of endogenous EPO and improving iron utilization to induce red blood cell regeneration from the core biological mechanism.

Indication under development
Chronic Kidney Disese (CKD) Anemia

Superiority

Best-in-class Potential: As a next-generation HIF-PHD inhibitor, ISM-4808 has demonstrated superior biochemical activity and efficacy in preclinical studies.
Nobel Prize-Validation Mechanism: By modulating the HIF-α signaling pathway, it simultaneously addresses the two core issues of anemia: EPO deficiency and impaired iron utilization.
Superior Pharmacological Propertise: Preclinical data confirms that ISM-4808 offers excellent oral absorption, no off-target risks, and stronger biological activity, which can significantly enhance patient compliance.

Marketplace

Explosive Market Growth:Taking the Mainland China market as an example, with over one million dialysis patients, the PHD inhibitor sector is showing robust momentum. The market size surged from RMB 50 million to RMB 2.5 billion within just five years (by 2024).

Shift from Injection to Oral Therapy:：Due to the convenience of oral administration and improved iron bioavailability, oral formulations are increasingly replacing traditional injectable drugs, becoming the mainstream trend in CKD anemia treatment.

Development

AI-Driven R&D Innovation: ISM-4808 exemplifies the breakthrough efficiency of AI-assisted drug discovery. Utilizing Insilico Medicine’s proprietary Chemistry42 generative AI engine, the structural design, synthesis, and testing were completed within just 12 months.
Academic Recognition: The research findings for this series were officially published in the prestigious Journal of Medicinal Chemistry in January 2024.
Clinical Trial Approval: The program received Investigational New Drug (IND) approval from China’s National Medical Products Administration (NMPA) Center for Drug Evaluation (CDE) in 2023.
Strategic In-Licensing: In December 2025, TaiGen Biotechnology officially in-licensed this program from Insilico Medicine Ltd. and Insilico Medicine IP Limited.