Evogene has announced acute Graft-Versus-Host Disease (aGVHD) as the target indication for its internal drug discovery programme, which aims to develop a potential first-in-class small-molecule therapy for patients who do not respond to steroid treatment following hematopoietic stem cell transplantation.

The programme will use Evogene’s proprietary ChemPass AI platform to design small-molecule candidates targeting a biological pathway associated with severe inflammation in steroid-refractory aGVHD. The company is working with clinical and scientific experts to advance the programme and address the unmet need for new treatment options.

Acute GVHD is a serious, potentially life-threatening complication of hematopoietic stem cell transplantation, affecting approximately 30–40 percent of transplant recipients. Mortality among patients with steroid-refractory aGVHD can reach 50 percent. Treatment options remain limited, with ruxolitinib currently the only approved second-line therapy, highlighting the need for additional targeted treatments.

Evogene reported that, within several months, it had generated a diverse series of novel, patentable small-molecule candidates featuring new chemical scaffolds and designed for synthetic feasibility. According to the company, the candidates demonstrate high potency at nanomolar concentrations, target selectivity, and favourable Absorption, Distribution, Metabolism and Excretion (ADME) and toxicology profiles.

Through its ChemPass AI platform, Evogene explored a virtual chemical space comprising more than 110 billion molecules. The platform enables the design of candidates with multiple drug-related properties optimised simultaneously, with the aim of accelerating discovery and identifying promising molecules beyond conventional screening of existing compound libraries.

The programme is guided by Dr. Corey Cutler of Dana-Farber Cancer Institute and Prof. Dr. Robert Zeiser of University Medical Center Freiburg. Their clinical and translational expertise is supporting target selection and the development strategy as Evogene advances its lead series towards investigational new drug (IND)-enabling studies.