• Oncology
• Other Therapeutic Areas

Oncology

Hypoxia Induced Factor (HIF)
The initial focus for clinical development of Ligon’s HIF Inhibitor Project is for renal cell carcinoma (RCC), due to unmet therapeutic need. In addition, HIF inhibitors have applications for other solid tumors, including pancreatic and lung cancers, in which HIF expression is aberrantly high and correlated with poor outcome. Moreover, HIF inhibitors have potential application for diabetic retinopathy, the most frequent cause of blindness in the U.S., affecting 65,000 individuals annually.

Ligon’s HIF Inhibitor Project is developing a first-in-class therapeutic for RCC and other solid tumors by targeting the Hypoxia-Induced Factor transcription factors (HIF) that control multiple pathways critical to the growth and survival of common cancers. Despite evidence that HIF is essential for the survival of certain cancer cells, no approved therapies directly target HIF.

There are 40,000 cases of RCC each year in the U.S. causing 12,000 deaths annually. 75% of RCCs are caused by inactivation of the VHL tumor suppressor gene, leading to constitutive activation of HIF. Existing therapies target the downstream consequences of HIF activation, specifically the VEGF angiogenic growth factor, but no therapies exist that directly target HIF.

The targeting of small-molecules directly to latent cytoplasmic transcription factors (TFs) such as HIF has not been accomplished, and until recently most TFs have been considered intractable for drug discovery. However, Ligon has successfully used SMM to identify inhibitors of HIF.

Other Oncology Targets
Ligon is also pursuing the development of small-molecule inhibitors that it has identified through SMM screening of transcription factors, chromatin-modifying enzymes and other highly-validated protein targets implicated in the development of cancers.